Risk Factors of Daunorubicine Induced Early Cardiotoxicity in Childhood Acute Lymphoblastic Leukemia: A Retrospective Study

Background: Daunorubicine, a type of anthracycline, is a drug commonly used in cancer chemotherapy that increases survival rate but consequently compromises with cardiovascular outcomes in some patients. Thus, preventing the early progression of cardiotoxicity is important to improve the treatment outcome in childhood acute lymhoblastic leukemia (ALL). Objective: The present study aimed to identify the risk factors in anthracycline-induced early cardiotoxicity in childhood ALL. Methods: This retrospective study was conducted by observing ALL-diagnosed children from 2014 to 2019 in Dr. Soetomo General Hospital. There were 49 patients who met the inclusion criteria and were treated with chemotherapy using Indonesian Childhood ALL Protocol 2013. Echocardiography was performed by pediatric cardiologists to compare before and at any given time after anthracycline therapy. Early cardiotoxicity was defined as a decline of left ventricle ejection fraction (LVEF) greater than 10% with a final LVEF < 53% during the first year of anthracycline administration.  Risk factors such as sex, age, risk stratification group, and cumulative dose were identified by using multiple logistic regression. Diagnostic performance of cumulative anthracycline dose was evaluated by receiver operating characteristic (ROC) curve. Results: Early anthracycline-induced cardiotoxicity was observed in 5 out of 49 patients. The median cumulative dose of anthracycline was 143.69±72.68 mg/m2. Thirty-three patients experienced a decreasing LVEF. The factors associated with early cardiomyopathy were age of ≥ 4 years (PR= 1.128; 95% CI: 1.015-1.254; p= 0.001), high risk group (PR= 1.135; 95% CI: 1.016-1.269; p= 0.001), and cumulative dose of ≥120 mg / m2 (CI= 1.161; 95% CI:1.019-1.332). Conclusion: Age of ≥ 4 years, risk group, and cumulative dose of ≥120 mg/m2 are significant risk factors for early cardiomyopathy in childhood ALL.     

Increased Risk of Thai Childhood Acute Lymphoblastic Leukemia with the MiR196a2 T>C Polymorphism

Objectives: This study assessed associations of the miR196a2 (rs11614913) T>C polymorphism withsusceptibility to childhood acute lymphoblastic leukemia (ALL) and clinical outcomes. Materials and Methods: Blood DNA samples from 104 childhood ALL patients and 180 healthy children were studied for the miR-196a2 (rs11614913) polymorphism using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) approach. Results: The frequency of the miR-196a2 (rs11614913) T allele in controls was 0.51 compared with 0.33 in ALL cases. In this study, CC, TC heterozygote and CC/TC genotypes were significantly associated with increase childhood ALL susceptibility compared with the TT wild type (OR =4.321, 95% CI = 2.091-8.930 p=0.000, OR = 2.248, 95% CI =1.103-4.579, p=0.024, OR = 2.921, 95% CI = 1.504-5.673 p=0.001, respectively). However, the miR-196a2 (rs11614913) T>C polymorphism was not associated with demographic data or clinico-pathological data in ALL cases. Conclusion: CC, TC and CC+TC genotypes of miR-196a2 (rs11614913) was significantly associated with increased susceptibility in Thai childhood ALL but not with clinical variables.     

The MTHFR C677T Polymorphism and Risk of Acute Lymphoblastic Leukemia: an Updated Meta-analysis Based on 37 Case-control Studies

Background: The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has beenassociated with acute lymphoblastic leukemia (ALL). However, results were conflicting. The aim of this studywas to quantitatively summarize the evidence for the MTHFRC677T polymorphism and ALL risk. Methods:Electronic searches of PubMed and the Chinese Biomedicine database were conducted to select case-control studiescontaining available genotype frequencies of C677T and the odds ratio (OR) with 95% confidence interval (CI)was used to assess the strength of any association. Results: Case-control studies including 6,371 cases and 10,850controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygousTT genotype had decreased risk of ALL (OR= 0.776, 95% CI: 0.687~0.877, p< 0.001) in Caucasians (OR= 0.715,95% CI: 0.655~0.781, p= 0.000). However, results among Asians (OR=0.711, 95% CI: 0.591~1.005, p= 0.055)and others (OR=0.913, 95% CI: 0.656~1.271, p= 0. 590) did not suggest an association. A symmetric funnelplot, the Egger’s test (P=0.093), and the Begg- test (P=0.072) were all suggestive of the lack of publication bias.Conclusion: This meta-analysis supports the idea that the MTHFR C677T genotype is associated with risk of ALLin Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbersof participants worldwide are needed to examine associations between the MTHFRC677T polymorphism andALL.     

Bone Mineral Density in Survivors of Childhood Acute Lymphoblastic Leukemia

Background: The objective of this study was to evaluate bone mineral density (BMD) after completion of treatment for childhood acute lymphoblastic leukemia (ALL). Methods: In this cross-sectional study, 103 survivors of ALL aged 13.5 ± 0.45 who completed their treatment at least one year earlier were enrolled. Among these, 49.5% and 51.5% received chemotherapy alone and chemotherapy plus cranial radiotherapy, respectively. Bone mineral content, BMD, and bone mineral apparent density in the lumbar spine (LS), femoral neck (FN) and forearm were assessed using dual-energy X-ray absorptiometry (DEXA). BMD Z-scores were classified according to International Society for Clinical Densitometry (ISCD) criteria. Results: The mean BMD Z-scores ± SD forLS, FN and forearm were -1.60 ± 0.12, -1.21 ± 0.9 and -2.43 ± 0.14 respectively with significant differences (P<0.001). Considering the lowest BMD Z-score in LS and FN areas (at any site) and according to the ISCD classification, 62.1%, 33% and 4.9% of the patients had normal BMD, low BMD and osteoporosis, respectively. Also, 8.7% of patients had developed fractures after completion of the treatment period, 4.9% having BMD Z-Scores Conclusions: ALL patients are at risk for low BMD and fracture. Therefore, applying DEXA scanning is recommended after completion of therapy for prevention of BMD reduction and osteoporosis.     

FHIT Gene Expression in Acute Lymphoblastic Leukemia and its Clinical Significance

Background: To investigate the expression of the fragile histidine triad (FHIT) gene in acute lymphoblastic leukemia and its clinical significance. Materials and Methods: The level of expressed FHIT mRNA in peripheral blood from 50 patients with acute lymphoblastic leukemia (ALL) and in 50 peripheral blood samples from healthy volunteers was measured via RT-PCR. Correlation analyses between FHIT gene expression and clinical characteristics (gender, age, white blood count, immunophenotype of acute lymphoblastic leukemia and percentage of blast cells) of the patients were performed. Results: The FHIT gene was expressed at 2.49±7.37 of ALL patients against 14.4±17.9 in the healthy volunteers. The difference in the expression levels between ALL patients and healthy volunteers was statistically significant. The rate of gene expression did not significantly vary with immunophenotype subtypes. Gene expression was also found to be correlated with increase of total leukocyte and decrease in platelets, but not with age, gender, immunophenotyping or percentage of blast cells. Conclusions: FHIT gene expression is low in acute lymphoblastic leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute lymphoblastic leukemia.     

Living Near Overhead High Voltage Transmission PowerLines as a Risk Factor for Childhood Acute LymphoblasticLeukemia: a Case-control Study

This study aimed to investigate association of living near high voltage power lines with occurrence of childhoodacute lymphoblastic leukemia (ALL). Through a case-control study 300 children aged 1-18 years with confirmedALL were selected from all referral teaching centers for cancer. They interviewed for history of living nearoverhead high voltage power lines during at least past two years and compared with 300 controls which wereindividually matched for sex and approximate age. Logistic regression, chi square and paired t-tests were usedfor analysis when appropriate. The case group were living significantly closer to power lines (P<0.001). Morethan half of the cases were exposed to two or three types of power lines (P<0.02). Using logistic regression, oddsratio of 2.61 (95%CI: 1.73 to 3.94) calculated for less than 600 meters far from the nearest lines against morethan 600 meters. This ratio estimated as 9.93 (95%CI: 3.47 to 28.5) for 123 KV, 10.78 (95%CI: 3.75 to 31) for230 KV and 2.98 (95%CI: 0.93to 9.54) for 400 KV lines. Odds of ALL decreased 0.61 for every 600 meters fromthe nearest power line. This study emphasizes that living close to high voltage power lines is a risk for ALL.     

Mutation Screening and Association Study of the Folylpolyglutamate Synthetase (FPGS) Gene with Susceptibility to Childhood Acute Lymphoblastic Leukemia

Background: Folylpolyglutamate synthetase (FPGS), an important enzyme in the folate metabolic pathway,plays a central role in intracellular accumulation of folate and antifolate in several mammalian cell types. Loss ofFPGS activity results in decreased cellular levels of antifolates and consequently to polyglutamatable antifolatesin acute lymphoblastic leukemia (ALL). Materials and Methods: During May 1997 and December 2003, 134children diagnosed with ALL were recruited from one hospital in Thailand. We performed a mutation analysis inthe coding regions of the FPGS gene and the association between single nucleotide polymorphisms (SNPs) withinFPGS in a case-control sample of childhood ALL patients. Mutation screening was conducted by polymerasechain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently with direct sequencing(n=72). Association analysis between common FPGS variants and ALL risk was done in 98 childhood ALL casesand 95 healthy volunteers recruited as controls. Results: Seven SNPs in the FPGS coding region were identifiedby mutation analysis, 3 of which (IVS13+55C>T, g.1297T>G, and g.1508C>T) were recognized as novel SNPs.Association analysis revealed 3 of 6 SNPs to confer significant increase in ALL risk these being rs7039798 (p=0.014, OR=2.14), rs1544105 (p=0.010, OR= 2.24), and rs10106 (p=0.026, OR= 1.99). Conclusions: These findingssuggested that common genetic polymorphisms in the FPGS coding region including rs7039789, rs1544105, andrs10106 are significantly associated with increased ALL risk in Thai children.     

Novel Mutations in the Displacement Loop of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia: A Genetic Sequencing Study

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children andrepresents approximately 25% of cancer diagnoses among those younger than 15 years of age. Materials andMethods: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA(mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblasticleukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of thed-loop region were amplified and successfully sequenced. Results: This revealed 132 mutations at 25 positionsin this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were allidentified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles wereobserved in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loopregion of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop ofmtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions(19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. Conclusions:Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acutelymphoblastic leukemia is recommended.     

Increased Risk of Childhood Acute Lymphoblastic Leukemia (ALL) by Prenatal and Postnatal Exposure to High Voltage Power Lines : A Case Control Study in Isfahan,Iran

Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies,accounting for one fourth of all childhood cancer cases. Exposure to environmental factors around the time ofconception or pregnancy can increase the risk of ALL in the offspring.This study aimed to evaluted the role ofprenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL.This cross-sectionalcase control study was carried out on 22 cases and 100 controls who were born and lived in low socioeconomicfamilies in Isfahan and hospitalized for therapeutic purposes in different hospitals from 2013-2014.With regardto the underlying risk factors, familial history and parental factors were noted but in this age, socioeonomic andzonal matched case control study, prenatal and childhood exposure to high voltage power lines was consideredas the most important environmental risk factors of ALL (p=0.006, OR=3.651, CI 95%, 1.692-7.878). As thepopulation was of low socioeconomic background, use of mobiles, computers and microwave was negligible.Moreover prenatal and postnatal exposure to indoor electrically charged objects was not determined to be asignificant environmental factor. Thus, pre and post natal exposure to high voltage power lines and living inpollutant regions as well as familial influence could be described as risk factors of ALL for the first time in alow socioeconomic status Iranian population     

Improved Outcomes of Childhood Acute Lymphoblastic Leukemia: A Retrospective Single Center Study in Saudi Arabia

Objective: Understanding the clinical and genetic characteristics of pediatric acute lymphoblastic leukemia (ALL) patients may help assigning the appropriate treatment. This study aims to understand patients’ characteristics, “real-world” treatment practice and outcomes of pediatric ALL. Methods: A cohort of 213 pediatric ALL patients, treated at (King Faisal Specialist Hospital and Research Center –Jeddah branch) KFSH and RC-J during the period of January 2002 to December 2015 were analyzed retrospectively. Statistical analyses were performed on patients’ demographic, clinical and genetics characteristics and outcomes of different treatment protocols. Survival was evaluated using Kaplan-Meier method, and differences in survival were tested using Log-Rank. Significance was set at 0.05 level. Results: Median age of the study cohort was 5 years (range 0.5–15 years) with 55.4% of male population. Majority of the patients had pre-B-cell ALL (88.7%), WBC count <50, 000/μL at diagnosis (76.1%, median = 13.5/μL with a range of 0.51–553.0/ μL) with involvement of central nervous system (CNS) disease in 8.5%patients.Different common chromosomal anomalies or abnormalities, including t(12, 21) translocation, MLL genre arrangements, trisomy (4, 10, 17)and others, were detected. Early response to the risk-directed treatment received by the patients (91.1% achieving <5% blast in the bone marrow) as well as the end of induction outcome (96.2%) was encouraging. Conclusion: We found that the patients’ clinical characteristics and distribution of genetic abnormalities were similar to those of the western countries. Our findings show that the earlier gap between the western countries and KSA in terms of survival has been closed and that competitive outcomes can be achieved with local infrastructure.     

Evaluation of MicroRNA92, MicroRNA638 in Acute Lymphoblastic Leukemia of Egyptian Children

Objective: miRNA considers a small non-coding RNA molecule that has tumor suppressor or oncogenic functions and regulates gene expression. miRNA may be involved in the pathogenesis of acute lymphoblastic leukemia (ALL).  miRNA was evaluated in patients with ALL to correlate their importance in the clinical prediction and the response to chemotherapy. Subject and methods: The study population included 30 healthy control and 71 children with ALL is divided into 4 groups: healthy, newly diagnosed, remitted, and relapsed groups. We quantify miRNA 92a, miRNA 638 expression using real-time PCR in childhood ALL. Results: plasma miRNA 92a and miRNA 638 expressions were elevated in ALL cases at the time of diagnosis (2.51 and 2.19 folds), and relapsed (2.1 and 1.61 folds) than that of patients with remitted ALL. There was a positive correlation between miRNA 92a and miRNA 638 patients with ALL. Also, total leukocyte and blast correlated with miRNA 92a and miRNA 638 unlike hemoglobin, and platelets didn’t correlate with miRNA 92a and miRNA 638. The sensitivity of miRNA 92a and miRNA 638 were 41.5% and 54.7% respectively while the specificity was 100 % of miRNA 92a and miRNA 638. Conclusion: miRNA 92a and miRNA 638 are recommended to be used as potential predictive and follow-up markers in children with ALL remitted and relapsed cases.     

Correlation of Inhibin and Several Antioxidants in Children with Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia (ALL) is most common in childhood. Inhibin (a non-steroidal glycoprotein hormone of gonadal origin) can be used as marker of fertility. The current study was conducted to evaluate inhibin levels in ALL patients and to estimate its correlation with some antioxidants in these in comparison with control subjects. Materials and Methods: This study was conducted on sixty patients with ALL and thirty children as controls. Fasting blood samples were taken from each subject and analyzed for haemoglobin, serum protein, vitamin E and C, in addition to glutathione and inhibin. Results: The results of the study showed highly significant decreases (p<0.001) in haemoglobin, glutathione and inhibin levels with significant decreases (p<0.05) in serum protein and vitamin E levels for patients group in comparison with controls while there was no significant differences in vitamin C. Moreover, there were significant correlations between inhibin levels and serum protein, glutathione and both vitamins (E and C) in the ALL patient group (r= 0.81, 0.80, 0.77 and 0.69, respectively). Conclusions: The present results indicated infertility in patients with ALL demonstrated by low inhibin level as a consequence of abnormality in anti-oxidative metabolism due to the cancer process. So, it can be suggested the need for routine measurement of inhibin for leukemic patients to estimate the action of hormones of gonadal origin.     

Comparison of Univariate and Multivariate Gene Set Analysisin Acute Lymphoblastic Leukemia

Background: Gene set analysis (GSA) incorporates biological with statistical knowledge to identify gene setswhich are differentially expressed that between two or more phenotypes. Materials and Methods: In this papergene sets differentially expressed between acute lymphoblastic leukaemia (ALL) with BCR-ABL and those withno observed cytogenetic abnormalities were determined by GSA methods. The BCR-ABL is an abnormal genefound in some people with ALL. Results: The results of two GSAs showed that the Category test identified 30gene sets differentially expressed between two phenotypes, while the Hotelling’s T2 could discover just 19 genesets. On the other hand, assessment of common genes among significant gene sets showed that there were highagreement between the results of GSA and the findings of biologists. In addition, the performance of these methodswas compared by simulated and ALL data. Conclusions: The results on simulated data indicated decrease inthe type I error rate and increase the power in multivariate (Hotelling’s T2) test as increasing the correlationbetween gene pairs in contrast to the univariate (Category) test.     

MDR1 C3435T and C1236T Polymorphisms: Association with High-risk Childhood Acute Lymphoblastic Leukemia

Background: MDR1, one of the most important drug-transporter genes, encodes P- glycoprotein (P-gp)-atransporter involved in protecting against xenobiotics and multi-drug resistance. The significance of the geneticbackground in childhood acute lymphoblastic leukemia (ALL) is not well understood. Materials and Methods:To evaluate whether C3435T and C1236T MDR1 polymorphisms are associated with the occurrence and outcomeof ALL, 208 children with ALL (median age 5.0 yr) and 101 healthy Thai children were studied by polymerasechain reaction-restriction fragment-length polymorphism (PCR-RFLP) assay. Results: C3435T and C1236TMDR1 polymorphism are significantly associated with the high-risk group (OR= 2.6, 95%CI =1.164-5.808; P=0.028 and OR= 2.231, 95%CI =1.068-4.659; p=0.047, respectively), indicating that both may be candidates formolecular markers in the high-risk group of ALL.     

Efficacy Oral Glutamine to Prevent Oral Mucositis and Reduce Hospital Costs During Chemotherapy in Children with Acute Lymphoblastic Leukemia

Objective: To investigate the use of glutamine administered orally during Methotrexate chemotherapy to prevent oral mucositis and reduce hospital costs in children with acute lymphoblastic leukemia (ALL). Methods: Twenty-four children received oral glutamine (400 mg/kg body weight per day) and twenty four received placebo on days of chemotherapy administration and for at least 14 additional days. Oral mucositis  was graded daily at each day of treatment till completion of therapy. The study groups were compared for the oral mucositis development using the WHO scale. Results: Oral mucositis occurred in 4.2 % of the glutamine group and 62.5% in the placebo group. The use of glutamine was directly associated with prevention of oral mucositis than placebo (OR 0,026; 95% CI: 0,003-0,228). The duration of length hospital stay was lower in the glutamine group than in the placebo group ((8 vs 12 days); p = 0,005). Hospital cost per day for glutamine group was 40 USD per day while placebo group was 48 USD per day. Conclusions: There was significant difference in the prevention of oral mucositis by oral glutamine vs placebo. The hospital cost for glutamine supplementation was lower than control group.     

Association of lnc-LAMC2-1:1 rs2147578 and CASC8 rs10505477 Polymorphisms with Risk of Childhood Acute Lymphoblastic Leukemia

Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding RNAs that are involved in a wide variety of biological processes. There are limited data regarding the impact of lnc-LAMC2-1:1 rs2147578 as well as CASC8 rs10505477 T>C polymorphisms on cancer development. Here we examined for the first time whether rs2147578 and rs10505477 polymorphisms are associated with childhood acute lymphoblastic leukemia (ALL) in a total of 110 cases and 120 healthy controls. Genotyping was achieved by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The rs2147578 variant increased the risk of ALL in codominant (OR=4.33, 95%CI=2.00-9.37, p<0.0001, CG vs CC, and OR=5.81, 95%CI=2.30-14.69, p=0.0002, GG vs CC), dominant (OR=4.63, 95%CI=2.18-9.86, p<0.0001, CG+GG vs CC), overdominant (OR=1.74, 95%CI=1.02-2.97, p=0.0444, CG vs CC+GG) and allele (OR=1.91, 95%CI=1.32-2.77, p=0.0008, G vs C) inheritance models tested. No significant association was found between the CASC8 rs10505477 T>C variant and risk of childhood ALL. In conclusion, the present study revealed that the lnc-LAMC2-1:1 rs2147578 polymorphism may be a risk factor for developing childhood ALL. Further studies with larger sample sizes with different ethnicities are now required to confirm our findings.     

Prognostically Significant Fusion Oncogenes in Pakistani Patients with Adult Acute Lymphoblastic Leukemia and their Association with Disease Biology and Outcome

Background and objectives: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. Methods: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL positive patients had frequent organomegaly and usually presented with a platelets count of less than 50 x109/l. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. Conclusions: This is the first study from Pakistan which investigated the frequency of 5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes weredifferent from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.     

Cytogenetic Profile of De Novo B lineage Acute Lymphoblastic Leukemia: Determination of Frequency,Distribution Pattern and Identification of Rare and Novel Chromosomal Aberrations in Indian Patients

Background: Chromosomal aberrations identified in acute lymphoblastic leukemia (ALL) have an importantrole in disease diagnosis, prognosis and management. Information on karyotype and associated clinical parametersare essential to physicians for planning cancer control interventions in different geographical regions. Materialsand Methods: In this study, we present the overall frequency and distribution patterns of chromosomal aberrationsin both children and adult de novo B lineage ALL Indian patients using conventional cytogenetics, interphaseFISH and multiplex RT-PCR. Results: Among the 215 subjects, cytogenetic results were achieved in 172 (80%)patients; normal karyotype represented 37.2% and abnormal 62.8% with a distribution as follows: 15.3%hypodiploidy; 10.3% hyperdiploidy; 15.8% t(9;22); 9.8% t(1;19); 3.7% t(12;21); 2.8% t(4;11); 2.8% complexkaryotypes. Apart from these, we observed several novel, rare and common chromosomal rearrangements. Also,FISH studies using LSI extra-signal dual-color probes revealed additional structural or numerical changes.Conclusions: These results demonstrate cytogenetic heterogeneity of ALL and confirm that the incidence ofchromosomal abnormalities varies considerably. To the best of our knowledge, this is one of the largest reportedseries of cytogenetic investigations in Indian B-lineage ALL cases. In addition, ongoing cytogenetic studies arewarranted in larger groups of B-lineage ALL cases to identify newly acquired chromosomal abnormalities thatmay contribute to disease diagnosis and management.