Childhood Leukaemia

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Leukaemia is the most common cancer of childhood. The body produces lymphocytes to protect the body from infection, in leukaemia these cells do not mature properly and become too numerous in the blood and bone marrow. Leukaemias may be acute or chronic. The most common type is acute lymphoblastic leukaemia (ALL). There are a number of other less common acute types which may be grouped together as acute non-lymphoblastic leukaemia (ANLL), this includes acute myeloid leukaemia (AML). This page contains links to information specifically related to Childhood Leukaemia, other relevant resources are available via the Main Menu of Children's Cancer Web

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Childhood Acute lymphoblastic leukaemia

Childhood Acute Myeloid Leukaemia

Information Patients and Family (7 links)

  Targeting cancer genes to treat childhood leukaemia


Leukaemia & Lymphoma Research
Dr Owen Williams talks about developing new drugs to treat childhood leukaemia. Dr Williams is from the UCL Institute of Child Health and Great Ormond Street Hospital for children NHS Trust.

 Childhood Leukemia

Children with Cancer UK
Overview of childhood leukaemia, with pages for specific types of leukaemia.

 Childhood Leukemia Foundation

A national non-profit organization which supports families and children with Leukemia.

 Leukaemia & Lymphoma Research

A national charity dedicated to research into blood cancers, including leukaemia, lymphoma and myeloma.

 Leukaemia Busters

This is a registered charity linked with Southampton General Hospital. It was founded in 1989 to raise money for research into leukaemia and lymphoma at the The Simon Flavell Leukaemia Research Unit.

 Leukaemia Foundation of Australia

 National Children's Leukemia Foundation

The NCLF is a non-profit organization providing services, support, and referrals for leukemia patients and their families.The site provides details of their telephone help line, and information on various topics related to childhood leukemia.

Information for Health Professionals / Researchers (4 links)

• PubMed search for publications about Childhood Leukaemia - Limit search to: [Reviews]

  PubMed Central search for free-access publications about Childhood Leukaemia
  MeSH term: Leukemia
  US National Library of Medicine
  PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.

 Childhood Leukaemia

Patient UK
PatientUK content is peer reviewed. Content is reviewed by a team led by a Clinical Editor to reflect new or updated guidance and publications. Further info.


 Childhood Leukaemia Investigation Prague - Čeština - English

CLIP
Includes details of research projects and publications.

 Leukemia

SEER, National Cancer Institute
Part of a SEER report on statistical trends and risk factors associated with childhood cancers. From: Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975-1995. (PDF)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Survival rates in subsets of pediatric patients who have acute myeloid leukemia (AML) with favorable risk features are now greater than 90%. However, outcomes for patients with high-risk (HR) features remain unacceptably poor. As novel technologies for the identification of HR biomarkers and the detection of residual disease are developed, risk stratification and the application of allogeneic hematopoietic stem cell transplant (HSCT) are evolving. HSCT has been shown to benefit subpopulations of pediatric patients with AML, including those with HR cytogenetic translocations, genetic mutations, and/or residual disease after induction. Targeted therapies have shown promise for improving outcomes, and their integration into standard therapy and HSCT regimens is a critical area of interest. Also, expansion of the donor pool has led to the successful use of alternative donor sources for those patients without a matched sibling. However, transplant-related morbidity and mortality and late effects are major limiting factors. Reduced-intensity conditioning regimens have resulted in outcomes equivalent to those achieved with myeloablative regimens among patients in complete remission. The limitation of transplant-related morbidity and mortality through reduced-intensity conditioning and supportive care, and improved survival through optimal alloreactivity in combination with targeted therapy, are steps toward advancing outcomes for pediatric patients who have AML with HR features.

Related: Acute Myeloid Leukemia (AML) Childhood Acute Myeloid Leukaemia AML - Molecular Biology Stem Cell and Bone Marrow Transplants

Introduction: One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore. Materials and Methods: A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed. Results: We identified 1124 cases of childhood cancers with a median follow-up of 3.49 (0 to 24.06) years. The most common primary malignancies were leukaemia (47.1%), central nervous system tumours (11.7%) and lymphoma (9.8%). Fifteen cases developed SMNs, most commonly acute myeloid leukaemia/myelodysplastic syndrome (n = 7). Median interval between the first and second malignancy was 3.41 (0.24 to 18.30) years. Overall 20-year cumulative incidence of SMNs was 5.3% (95% CI, 0.2% to 10.4%). The 15-year cumulative incidence of SMNs following acute lymphoblastic leukaemia was 4.4% (95% CI, 0% to 8.9%), significantly lower than the risk after osteosarcoma of 14.2% (95% CI, 0.7% to 27.7%) within 5 years (P <0.0005). Overall 5-year survival for SMNs was lower than that of primary malignancies. Conclusion: This study identified factors explaining the epidemiology of SMNs described, and found topoisomerase II inhibitor use to be a likely risk factor in our cohort. Modifications have already been made to our existing therapeutic protocols in osteosarcoma treatment. We also recognised the importance of other risk management strategies, including regular long-term surveillance and early intervention for detected SMNs, to improve outcomes of high risk patients.

Related: Bone Cancers Brain and Spinal Cord Tumours Acute Myeloid Leukemia (AML) Cancer Prevention and Risk Reduction Osteosarcoma

We examined the possible relationship between three RAGE polymorphisms, -429C/T, -374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE -374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.

Related: Polymorphisms Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

T-Acute Lymphoblastic Leukemia (T-ALL) remains a subgroup of pediatric ALL, with a lower response to standard chemotherapy. Some recent studies established the fundamental role of epigenetic aberrations such as DNA hypermethylation, to influence patients' outcome and response to chemotherapy. Moreover, L-asparaginase is an important chemotherapeutic agent for treatment of ALL and resistance to this drug has been linked to ASNS expression, which can be silenced through methylation. Therefore, we tested whether the sensitivity of T-ALL cell lines towards L-asparaginase is correlated to the epigenetic status of ASNS gene and whether the sensitivity can be modified by concurrent demethylating treatment. Hence we treated different T-ALL cell lines with L-asparaginase and correlated different responses to the treatment with ASNS expression. Then we demonstrated that the ASNS expression was dependent on the methylation status of the promoter. Finally we showed that, despite the demethylating effect on the ASNS gene expression, the combined treatment with the demethylating agent Decitabine could synergistically improve the L-asparaginase sensitivity in those T-ALL cell lines characterized by hypermethylation of the ASNS gene. In conclusion, this preclinical study identified an unexpected synergistic activity of L-asparaginase and Decitabine in the subgroup of T-ALL with low ASNS expression due to hypermethylation of the ASNS promoter, while it did not restore sensitivity in the resistant cell lines characterized by higher ASNS expression.

Related: Azacitidine

BACKGROUND: Childhood acute lymphoblastic leukaemia (ALL) survivors have an increased risk of metabolic and cardiovascular disease. We aimed to assess the presence of non-alcoholic fatty liver disease (NAFLD) in childhood ALL and if it is associated with early cardiovascular dysfunction.
METHODS: In total, 53 childhood ALL survivors and 34 controls underwent auxological evaluation, biochemical assay, liver, heart and vascular ultrasound study.
RESULTS: NAFLD was more frequent in ALL patients than in controls (39.6% vs 11.7%, P < 0.01). Patients with NAFLD were more obese and insulin resistant than patients without NAFLD. Flow-mediated dilatation and interventricular septum were lower in the ALL group than those in the control group (P < 0.001 for both). The patients with NAFLD showed lower left ventricular ejection fraction than those without NAFLD (P = 0.011). In ALL survivors, BMI-SDS and subcutaneous fat were the strongest predictors of NAFLD, whereas preperitoneal adipose tissue and C-reactive protein were the strongest predictors of left ventricular ejection fraction.
CONCLUSIONS: Childhood ALL survivors had higher prevalence of NAFLD than healthy controls, which is associated with early left ventricular impairment. In the case of fatty liver, a comprehensive heart evaluation is mandatory. We strongly recommend to prevent visceral adiposity in ALL survivors, to search for metabolic syndrome or its components and to reinforce the need of intervention on diet and lifestyle during the follow-up of these patients.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

Childhood acute lymphoblastic leukemia (ALL) occurs more frequently in males. Reasons behind sex differences in childhood ALL risk are unknown. In the present genome-wide association study (GWAS), we explored the genetic basis of sex differences by comparing genotype frequencies between male and female cases in a case-only study to assess effect-modification by sex.The case-only design included 236 incident cases of childhood ALL consecutively recruited at the Texas Children's Cancer Center in Houston, Texas from 2007 to 2012. All cases were non-Hispanic whites, aged 1 to 10 years, and diagnosed with confirmed B-cell precursor ALL. Genotyping was performed using the Illumina HumanCoreExome BeadChip on the Illumina Infinium platform. Besides the top 100 statistically most significant results, results were also analyzed by the top 100 highest effect size with a nominal statistical significance (P <0.05).The statistically most significant sex-specific association (P = 4 × 10) was with the single nucleotide polymorphism (SNP) rs4813720 (RASSF2), an expression quantitative trait locus (eQTL) for RASSF2 in peripheral blood. rs4813720 is also a strong methylation QTL (meQTL) for a CpG site (cg22485289) within RASSF2 in pregnancy, at birth, childhood, and adolescence. cg22485289 is one of the hypomethylated CpG sites in ALL compared with pre-B cells. Two missense SNPs, rs12722042 and 12722039, in the HLA-DQA1 gene yielded the highest effect sizes (odds ratio [OR] ∼ 14; P <0.01) for sex-specific results. The HLA-DQA1 SNPs belong to DQA1*01 and confirmed the previously reported male-specific association with DQA1*01. This finding supports the proposed infection-related etiology in childhood ALL risk for males. Further analyses revealed that most SNPs (either direct effect or through linkage disequilibrium) were within active enhancers or active promoter regions and had regulatory effects on gene expression levels.Cumulative data suggested that RASSF2 rs4813720, which correlates with increased RASSF2 expression, may counteract the suppressor effect of estrogen-regulated miR-17-92 on RASSF2 resulting in protection in males. Given the amount of sex hormone-related mechanisms suggested by our findings, future studies should examine prenatal or early postnatal programming by sex hormones when hormone levels show a large variation.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology RASSF2

OBJECTIVES: Invasive aspergillosis (IA) is an important cause of mortality and morbidity in children with hematological malignancies. The monitoring of serum galactomannan (GM) antigen is considered useful in the diagnosis of IA . The aim of this study was to determine the utility of serum GM monitoring in the early diagnosis of IA and the role of positive antigenemia in the management of children with acute lymphoblastic leukemia (ALL).
METHODS: The cases of 141 children who were being treated for ALL in the Division of Pediatric Hematology of the Medical School of Ege University between January 2006 and February 2015 were reviewed retrospectively. Cases of proven and probable IA were defined according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria.
RESULTS: The incidence of proven and probable IA was 3.5% (5/141). The incidence of positive GM antigenemia among 3264 serum samples was 5.5% (n=179). Of the cases detected, 21.7% were true-positive, 52.1% were false-positive, and the remaining 26.1% were classified as 'undetermined.' An increase in the incidence of true-positive tests and induction of antifungal therapy was determined through multiple consecutive positive tests.
CONCLUSIONS: GM may be detected in the serum before the clinical signs of IA appear, but its sensitivity and specificity are variable. False-positivity is a significant disadvantage, and consecutive positive GM must be taken into account in the case of clinical and imaging findings that are relevant to IA.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

Individualized therapy is a recent approach aiming to specify dosage regimen for each patient according to its genetic state. Cancer chemotherapy requires continuous monitoring of the plasma concentration levels of active forms of cytotoxic drugs and subsequent dose adjustment. In order to attain optimum therapeutic efficacy, correlation to pharmacogenetics data is crucial. In this study, a specific, accurate and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) has been developed for determination of methotrexate (MTX), 6-mercaptopurine (MP) and its metabolite 6-thioguanine nucleotide (TG) in human plasma. Based on the basic character of the studied compounds, solid phase extraction using a strong cation exchanger was found the optimum approach to achieve good extraction recovery. Chromatographic separation was carried out using RP-HPLC and isocratic elution by acetonitrile: 0.1% aqueous formic acid (85:15v/v) with a flow rate of 0.8mL/min at 40°C. The detection was performed by tandem mass spectrometry in MRM mode via electrospray ionization source in positive ionization mode. Analysis was carried out within 1.0min over a concentration range of 6.25-200.00ng/mL for the studied analytes. Validation was carried out according to FDA guidelines for bioanalytical method validation and satisfactory results were obtained. The applicability of the assay for the monitoring of the MTX, MP and TG and subsequent application to personalized therapy was demonstrated in a clinical study on children with acute lymphoblastic leukemia (ALL). Results confirmed the need for implementation of reliable analysis tools for therapeutic dose adjustment.

Related: Mercaptopurine Methotrexate Polymorphisms Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology Tioguanine

Acute leukemia is the most common childhood cancer diagnosis and leading cause of cancer-related death among children and adolescents. Despite substantial improvements in the survival rate of childhood acute leukemia, approximately 20-40% of the patients who undergo treatment develop relapse, with a dismal one third of these patients surviving in the long term. Epigenetics plays an important role in the progression of cancer, and existing evidence suggests a role in childhood acute leukemia relapse. A better understanding of the epigenetic mechanisms in recurrent acute leukemia could potentially lead to novel therapeutic regimens to prevent or treat disease recurrences. In this review, we summarize existing evidence on two of the most studied epigenetic mechanisms, DNA methylation and microRNA expression, in recurrent pediatric acute leukemia.

Related: MicroRNAs

BACKGROUND: Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related receptor kinase B (TrkB) are involved in the maturation of B lymphocytes in the bone marrow (BM), promote cell differentiation in B-cell malignancies, and are associated with poor prognosis in adults with acute leukemia (AL). However, the role of BDNF in pediatric AL remains poorly understood.
OBJECTIVE: We carried out a cohort observational study to evaluate BDNF levels in BM or peripheral blood (PB) samples from children with AL.
METHODS: BM or PB samples were collected from 57 children and adolescents with acute lymphoid leukemia (ALL), 14 children and adolescents with acute myeloid leukemia (AML), and 44 healthy individuals (HI) of the same age range.
RESULTS: BDNF levels at diagnosis in AL patients were significantly lower when compared to HI. Samples from patients in complete remission from disease had higher levels of BDNF compared to those obtained from patients with malignant cells. Moreover, BDNF levels at diagnosis in patients who died were significantly lower compared to those found in survivors.
CONCLUSIONS: These findings provide the first evidence for a possible role of BDNF as a marker of active disease and poor prognosis in pediatric AL.

Related: Acute Myeloid Leukemia (AML) Childhood Acute Myeloid Leukaemia AML - Molecular Biology Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

AIM: Up-regulation of metalloproteinase (MMPs) proteins have been shown in various types of solid cancers and the genotype of MMP1 has been associated with the risk of solid cancers. However, the contribution of MMP1 genotype to leukemia has never been investigated to our knowledge. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan.
MATERIALS AND METHODS: In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology.
RESULTS: The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter rs1799750 genotype was 49.2%, 39.5% and 11.3% in the childhood ALL group and 36.8%, 43.6% and 19.5% in the non-cancer control group, respectively (p for trend=0.0046), significantly differentially distributed between childhood ALL and control groups. The carrier comparisons in dominant and recessive models also support the findings that 1G appears to be the protective allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP1 rs1799750 1G/2G or 1G/1G genotypes had lower odds ratios(ORs) of 0.68 and 0.43 [95% confidence intervals (CI)=0.47-0.98 and 0.26-0.73, p=0.0395 and 0.0013, respectively] for childhood ALL than those carrying the 2G/2G genotype. Analysis of genotype inaction with age of onset age showed those aged less than 3.5 years at onset carrying the 1G/2G or 1G/1G genotypes had lower ORs (0.0183 and 0.0004, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more.
CONCLUSION: Our results indicate that the MMP1 rs1799750 1G allele is a protective biomarker for childhood ALL.

Related: MMP1 Acute Lymphocytic Leukemia (ALL)

BACKGROUND: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy.
CASE SUMMARY: We report a case of a 15-year-old boy with a fatal systemic ADV infection. He had received reinduction chemotherapy for relapsed acute lymphoblastic leukemia under continuing antifungal therapy for previously diagnosed fungal pneumonia. He complained of fever and right shoulder pain 4 days after completing the reinduction chemotherapy. In spite of appropriate antibiotic and antifungal therapy, pneumonia was aggravated and gross hematuria was accompanied. A multiplex polymerase chain reaction test for respiratory viruses was positive for ADV in a blood sample, and a urine culture was positive for ADV. He received oral ribavirin, intravenous immunoglobulin, and intravenous cidofovir therapy; however, he eventually died. Relapsed leukemia, concurrent fungal pneumonia, and delayed cidofovir administration were considered the cause of the grave outcome in this patient.
CONCLUSION: ADV may cause severe infections not only in allogeneic hematopoietic cell transplant recipients, but also in patients undergoing chemotherapy for acute leukemia. The risk factors for severe ADV infection in patients undergoing chemotherapy should be determined in the future studies, and early antiviral therapy should be administered to immune compromised patients with systemic ADV infection.

Related: Acute Lymphocytic Leukemia (ALL)

BACKGROUND: Genetic polymorphisms in patients with acute lymphoblastic leukemia (ALL) may influence the toxicity of chemotherapeutic agents. Due to the importance of the transport P-glycoprotein and methylenetetrahydrofolate reductase in the metabolism of chemotherapeutic agents, we analyzed the MDR1 rs1045642 and MTHFR rs1801133 polymorphisms and their associations with clinical outcomes in Mexican childhood ALL patients.
METHODS: A total of 109 patients participated in this study. The clinical evaluation consisted of a physical examination and a laboratory test. Genotyping of MDR1 rs1045642 (3435 C>T) and MTHFR rs1801133 (677 C>T) was performed by polymerase chain reaction/restriction fragment length polymorphism. Statistical analyses were performed using SPSS 14.0. The odds ratios and 95% confidence intervals (CI) were estimated by logistic regression.
RESULTS: Individuals who were CC homozygotes at MDR1 rs1045642 had lower risk of having methotrexate plasma concentrations >1 μM and leukopenia grade I (odds ratio [OR] = 0.30; 95% CI = 0.13-0.72 and OR = 0.32; 95% CI = 0.14-0.72, respectively). Patients who were CC homozygotes at MTHFR rs1801133 had a higher risk of developing mucositis (OR = 3.61; 95% CI = 1.42-9.14).
CONCLUSION: MDR1 rs1045642 and MTHFR rs1801133 should be considered as diagnostic candidates for the identification of pediatric patients with a high risk of suffering adverse events during ALL treatment.

Related: Methotrexate Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology MTHFR

BACKGROUND/AIMS: Acute and chronic leukemia are severe malignant cancers worldwide, and can occur in pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia (PL) remains challenging. Autophagy is essential for the regulation of cell survival in the harsh environment. However, the role of autophagy in the survival of PL cells under the oxidative stress, e.g. chemotherapy, remain ill-defined. In the current study, we addressed these questions.
METHODS: We analyzed the effects of oxidative stress on the cell viability of PL cells in vitro, using a CCK-8 assay. We analyzed the effects of oxidative stress on the apoptosis and autophagy of PL cells. We analyzed the levels of Beclin-1 and microRNA-93 (miR-93) in PL cells. Prediction of binding between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The relationship between levels of miR-93 and patients' survival was analyzed in PL patients.
RESULTS: We found that oxidative stress dose-dependently increased autophagy in PL cells. While low-level oxidative stress did not increase apoptosis, high-level oxidative stress increased apoptosis, seemingly from failure of autophagy-mediated cell survival. High-level oxidative stress appeared to suppress the protein levels of an autophagy protein Beclin-1 in PL cells, possibly through induction of miR-93, which inhibited the translation of Beclin-1 mRNA via 3'-UTR binding.
CONCLUSION: Beclin-1-mediated autophagy plays a key role in the survival of PL cells against oxidative stress. Induction of miR-93 may increase the sensitivity of PL cells to oxidative stress during chemotherapy to improve therapeutic outcome.

Related: MicroRNAs Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology Signal Transduction

PURPOSE: The aim of this study was to investigate roles of microRNA (miR)-183 in pediatric acute myeloid leukemia (AML).
METHODS: miR-183 expression in bone marrow and patients' sera of childhood AML was detected by real-time quantitative PCR. Functions of miR-183 in malignant phenotypes of two leukemia cell lines were then evaluated. Additionally, putative targets of miR-183 were predicted using three miRNA target prediction algorithms and validated by luciferase reporter assay. Clinical relevance of miR-183 and its target gene were further determined.
RESULTS: miR-183 expression in bone marrow and patients' sera of childhood AML was both significantly higher than those in the corresponding normal controls (both P < 0.001). Enforced expression of miR-183 dramatically enhanced cell proliferation and G1/S transition, but inhibited cell apoptosis of leukemia cells. Bioinformatics prediction and luciferase reporter assay identified programmed cell death 6 (PDCD6) as a direct target gene of miR-183. Moreover, high serum miR-183 combined with low serum PDCD6 mRNA was significantly associated with French-American-British classification subtype M7 (P = 0.01) and unfavorable karyotypes (P = 0.006). Further multivariate analysis identified the combination of serum miR-183 and PDCD6 levels as an independent prognostic factor for both relapse-free and overall survivals. Functionally, re-introduction of PDCD6 markedly reversed the effects of miR-183 in cell cycle, proliferation and apoptosis of two leukemia cell lines.
CONCLUSION: Combined serum miR-183 and PDCD6 mRNA may serve as a novel prognostic biomarker for pediatric AML. Interestingly, miR-183 may function as an oncogene and may enhance cell proliferation by targeting PDCD6, implying a potential therapeutic target for this malignancy.

Related: Apoptosis Acute Myeloid Leukemia (AML) Childhood Acute Myeloid Leukaemia AML - Molecular Biology MicroRNAs PDCD6

Cytogenetic analyses (karyotype and, if necessary, appropriate complementary FISH analyses) are mandatory at diagnosis in acute lymphoblastic leukemia (ALL) as their results are taken into account in therapeutic protocols due to their diagnostic and prognostic values. In some cases, karyotype can be completed by other techniques (RT-PCR, RQ-PCR, DNA content, SNP-array, MLPA…) that can be equally or more informative than FISH. Here, we have tempted to establish guidelines concerning karyotype and FISH analyses according to the most recent data of the litterature which is reviewed here, completing the 2008 WHO classification with the recent new cytogenomic entities such as Ph-like ALL and indicating possible therapeutic implications.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous genetic disease and its etiology remains poorly understood. Recent genome wide association and replication studies have highlighted specic polymorphisms contributing to childhood ALL predispositions mostly in European populations. It is unclear if these observations generalize to other populations with a lower incidence of ALL. The current case-control study evaluated variants in ARID5B (rs7089424, rs10821936), IKZF1 (rs4132601) and CEBPE (rs2239633) genes, which appear most significantly associated with risk of developing childhood B-lineage ALL.
MATERIALS AND METHODS: Using TaqMan assays, genotyping was conducted for 162 de novo B-lineage ALL cases and 150 unrelated healthy controls in India. Appropriate statistical methods were applied.
RESULTS: Genotypic and allelic frequencies differed significantly between cases and controls at IKZF1-rs4132601 (p=0.039, p=0.015) and ARID5B-rs10821936 (p=0.028, p=0.026). Both rs10821936 (p=0.019; OR 0.67; 95% CI=0.47-0.94) and rs4132601 (p=0.018; OR 0.67; 95%CI 0.48-0.94) were associated with reduced disease risk. Moreover, gender- analysis revealed male-specific risk associations for rs10821936 (p=0.041 CT+CC) and rs4132601 (p=0.005 G allele). Further, ARID5B-rs7089424 and CEBPE-rs2239633 showed a trend towards decreased disease risk but without significance (p=0.073; p=0.73).
CONCLUSIONS: Our findings provide the rst evidence that SNPs ARID5B- rs10821936 and IKZF1-rs4132601 are associated with decreased B-lineage ALL susceptibility in Indian children. Understanding the effects of these variants in different ethnic groups is crucial as they may confer different risk of ALL within different populations.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology ARID5B

The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our findings indicated that promoter methylation of TET2 significantly increases the risk of ALL (OR=2.60, 95% CI=1.31-5.12, p=0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was significantly downregulated in childhood ALL compared to healthy children (p=0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to confirm our findings.

Related: Acute Lymphocytic Leukemia (ALL) TET2

A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis.

Related: Crisantaspase Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

BACKGROUND: Preterm birth (PTB) has been recognized as a crucial long term risk factor for multiple non-communicable diseases. However, studies between the relationship of PTB and the risk of acute childhood leukemia have yielded inconclusive results. Therefore, we performed a meta-analysis to systematically review the current literature to investigate whether PTB is associated with increased risk of acute childhood leukemia.
METHODS: Three electronic databases (PubMed, Web of Science, and EMBASE) were searched up to December 1st, 2015. Relevant studies reporting the association between PTB and subsequent risk of acute childhood leukemia were included for further evaluation. Statistical analysis was performed using Revmen 5.3 and Stata 10.0.
RESULTS: A total of 12 studies for acute childhood leukemia, eight studies for acute lymphoblastic leukemia (ALL), and seven studies for acute myeloid leukemia (AML) were included in the current meta-analyses. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate the relationship between PTB and acute childhood leukemia as well as its two subtypes: ALL and AML. Our results suggested that PTB was significantly associated with increased risk of acute childhood leukemia (OR = 1.09, 95% CI = 1.02-1.17, P = 0.01) and AML (OR = 1.42, 95% CI = 1.21-1.67, P < 0.01). However, PTB was not significantly associated with an increased risk of ALL (OR = 1.04, 95% CI = 0.96-1.13, P = 0.29).
CONCLUSION: Our data showed that PTB increased the risk of AML. Further studies are required to explore causality and dissect the biological mechanisms involved.

Related: Acute Myeloid Leukemia (AML) Acute Lymphocytic Leukemia (ALL)

Acute leukemia, especially acute lymphoblastic leukemia, is the most common tumor in childhood. Survival in pediatric acute leukemia cases has improved significantly, but once a relapse occurs, the long-term survival rates decrease markedly. Recently, SNP array and next-generation sequencing have revealed the relapse mechanism of pediatric leukemia and genetic alterations which drive leukemia recurrence.

Related: Acute Myeloid Leukemia (AML) Childhood Acute Myeloid Leukaemia AML - Molecular Biology Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

Numerous efforts have been made to elucidate the roles of individual genetic background factors in the risk of childhood acute lymphoblastic leukemia. Most have taken the form of case-control studies focusing on specific candidate gene polymorphisms. Recently, a more rigorous and comprehensive approach referred to as a genome-wide association study (GWAS) has been widely utilized and has achieved success. Case-control studies evaluating candidate gene associations have shown cumulative evidence of a role for folate metabolism and xenobiotic metabolism/transport pathway genetic variants. In addition, single nucleotide polymorphism (SNP)s identified by GWAS appear to indicate a strong role for genes encoding transcription factors involved in cellular differentiation. Further studies are needed to clarify the accumulating evidence obtained from both candidate gene and genome-wide investigations.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

OBJECTIVES: Acute lymphoblasstic leukemia (ALL) is the most common childhood malignancy. Prominin-1 is a cell-surface trans-membrane glycoprotein expressed on the stem cell surface and has potential role in diagnostic and prognostic work-up of several stem cell cancers. Aim of this Work: To assess the prognostic value of Prominin-1 expression in Egyptian children with ALL.
SUBJECTS AND METHODS: This study was conducted on 80 Egyptian children with newly diagnosed ALL and 30 healthy children of matched age and sex as a control group. Patient history, and clinical and laboratory examination results were taken, including complete blood count, serum LDH, bone marrow aspiration with cytochemistry, immunophenotyping, Fluorescent In Situ Hybridization technique for detection of t(9;22) and Flow cytometery for estimation of Prominin-1 expression on blast cells.
RESULTS: No statistically significant differences were observed between Prominin-1 positive and negative patients regarding age, sex and clinical presentation at diagnosis. No statistically significant differences between Prominin-1 positive and negative patients were observed regarding white blood cells and platelet counts, peripheral blood and bone marrow blast cells percentage while there were significantly higher hemoglobin and LDH levels in Prominin-1 positive patients. There were no significant differences between Prominin-1 positive and negative patients regarding immunophenotyping and t(9;22). There were statistically significant differences in disease outcome between Prominin-1 positive and negative expression with higher rate of relapse and death and lower rate of complete remission in patients with Prominin-1 positive expression (14 cases with Prominin-1 positive relapsed versus 2 cases with Prominin-1 negative, 12 cases with Prominin-1 positive died versus 2 cases with Prominin-1 negative and complete remission occurred in 20 cases with Prominin-1 positive versus 30 cases with Prominin-1 negative) (P =0.017). There was statistically significant difference in disease-free survival (P = 0.0072) and overall survival (P = 0.0424) between ALL patients with Prominin-1 positive and Prominin--1 negative expression.
CONCLUSION: Prominin-1 is a helpful prognostic marker in patients with ALL; therefore, it should be routinely assessed at diagnosis in ALL patients for better prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patient-specific risk factors.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

BACKGROUND: Identification of aberrant antigen expression is important in characterizing neoplastic population among non.neoplastic bone marrow counterparts and further in the detection of minimal residual disease. (MRD). Flow cytometry (FCM) is an important tool in identifying aberrant phenotypes. Incidence of aberrant phenotypes varies considerably in independent studies and its association with prognostic factors is still debatable.
AIM: To identify the prevalence of aberrant phenotypes on immunophenotyping in a large series of de novo acute lymphoblastic leukemia (ALL) and to evaluate any association with initial clinical and hematological features.
MATERIALS AND METHODS: In the current study, 303 patients of de novo ALL were included from the Department of Hematology, PGIMER, Chandigarh during the time period (July 2010 to June 2012). The immunophenotype of all cases of ALL was studied using FCM.
RESULTS: Aberrant myeloid antigen expression was seen in 42.5% cases. Most frequent aberrant myeloid antigen was CD13 (32.2% cases), followed by CD33 (27.2% cases) and CD117 (18.5% cases). The expression of CD117 was relatively frequent in comparison to earlier reports which describe its rare expression. Adult T- ALL showed higher expression of CD33 and CD117 than pediatric T-ALL (P = 0.032 and 0.043, respectively). Myeloid antigen expression in ALL was associated with lower WBC count (P < 0.05) and lower number of peripheral blasts (P < 0.05). Expression of CD34 was higher in My + ALL group (P < 0.05) than My- ALL group.
CONCLUSION: In summary, CD117 is a relatively frequently expressed myeloid marker contrary to earlier reports which describes its rare expression. Pediatric and adult ALL cases with low blast count and CD34 positivity are more likely to express aberrant myeloid markers. Current study also supports that myeloid antigen expression in both adult and pediatric ALL is not associated with adverse presenting clinical and biological features.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology

The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 × per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML.

Related: Acute Myeloid Leukemia (AML) Childhood Acute Myeloid Leukaemia AML - Molecular Biology

The purpose of the study was to assess the effect of the internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) on the outcome in pediatric acute myeloid leukemia (AML) patients. We identified eligible studies from several databases including PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) (from January 1995 to July 2015). Ten studies of 1661 pediatric patients with AML were included in exploring the relationship between the FLT3-ITD and overall survival (OS)/event free survival (EFS). Pediatric patients with AML with FLT3-ITD had worse OS [HR = 2.19 (1.60-3.01)]/EFS [HR = 1.70 (1.37-2.11)] than those patients without FLT3-ITD. Furthermore, FLT3-ITD had unfavorable effect on OS/EFS in the subgroups of NOS, uni/multivariate model, number of patients, the length of following-up, and patient source. The findings of this meta-analysis indicated that FLT3-ITD had negative impact on pediatric patients with AML.

Related: Acute Myeloid Leukemia (AML) Childhood Acute Myeloid Leukaemia AML - Molecular Biology FLT3

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