Childhood B-acute lymphoblastic leukemia: a genetic update

Woo, Jennifer S; Alberti, Michael O.; Tirado, Carlos A

doi:10.1186/2162-3619-3-16

Cited by 111 publications

(103 citation statements)

References 111 publications

(133 reference statements)

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“…The recurrent genetic abnormalities that are encountered in patients with B-cell ALL, the common genes that are implicated as well as the prognostic significance of these genetic abnormalities are shown in Table 4 [33,58,59]. Various studies have shown that the following molecular abnormalities occur in patients with ALL: BCR-ABL1, ATM, MLL, TCRα, TCRβ, HOX11, HOX11L2, CDKN2A, CDKN2B, TAL1, TAL2, C-MYC, CRLF2, IKZF1, JAK2, CASP8AP2, IgH/BCL11B, NUP214-ABL, miR15, miR16, TCF3-PBX1, E2A-HLF, ETV6-RUNX1, EBF1, RB1, CREBBP1, SETD2, FOXO3A, KMT2A (MLL), EPHA7, GRIK2, BLIMP1 and FYN [60][61][62].…”

Section: Molecular and Cytogenetic Abnormalities In All Patientsmentioning

confidence: 99%

“…Several studies have shown that the poor prognostic feature in patients with ALL are: (1) age ˂ 2 years or above 50 years, (2) WBC count ≥ 50 × 10 9 /liter, (3) presence of extramedullary disease, particularly CNS involvement, at presentation, (4) presence of residual disease following induction chemotherapy (≥ 5% BM blasts on days 15, 19,29,35 and 43), (5) unfavorable immunophenotypic profiles: precursor T, pro-B and mature B-cell types, and (6) presence of adverse or unfavorable cytogenetic abnormalities or molecular mutations such as: hypodiploidy with ˂ 44 chromosomes, near hypodiploidy, translocation (t) 4,11 (q21;q23), t8,14 (q24;q32), complex cytogenetics, MLL gene rearrangement, FLT 3 (13q12) mutation, BCR-ABL1-like (IKZF1, CRLF2 and JAK mutations), iAMP21 (RUNX1/P2RY8-CRLF2), and IgH (14q32) rearrangement with multiple fusion partners [61,63,114,115,117]. Also, several studies have shown that the following factors are associated with good prognosis in patients with ALL: (1) age between 2 and 10 years, (2) high hyperdiploidy, (3) del (9q), and t12,21 (p13;q22) (ETV6-RUNX1; TEL-AML1) [63,114,115,117].…”

Section: Prognosis and Risk Stratification In Allmentioning

confidence: 99%

“…Risk factors for relapse in ALL include: (1) WBC count > 100 × 10 9 /liter, and (2) having genes that express drug resistance such as: MLL-AF4, TEL-AML1, BCR-ABL and NT5C2 mutations that are associated with resistance to 6-mercaptopurine and 6-thioguanine [52,53]. In patients with B-cell ALL, genetic mutations that are associated with HR of treatment failure and relapse include: CDKN2A, CDKN2B, ETV6, IKAROS-IKZF1, CREBBP, SETD2, KDM6A, MSH6 and MLL2 [117]. The genetic mutations that are associated with relapse in patients with T-cell ALL include: TP53, KRAS, NRAS, NT5C2, USP7, IL7R, CNOT3 and MSH6 [119].…”

Section: Drug Resistance and Relapse In All Patientsmentioning

confidence: 99%

“…Also, several studies have shown that the following factors are associated with good prognosis in patients with ALL: (1) age between 2 and 10 years, (2) high hyperdiploidy, (3) del (9q), and t12,21 (p13;q22) (ETV6-RUNX1; TEL-AML1) [63,114,115,117]. However, intermediate outcome is associated with the following factors: (1) adolescents and young adults, (2) t9,22 (q34;q11), and (3) t1,19 (q23;p13) [63,115,117].…”

Section: Prognosis and Risk Stratification In Allmentioning

confidence: 99%

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Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

Wk¹,

Dridi²,

Ka³

2017

J Mol Genet Med

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The recent improvements in the outcomes of patients with acute lymphoblastic leukemia reflect the progress in the field of diagnostics and the achievements in therapeutic interventions. In particular, the availability of more advanced technology in the cytogenetic and molecular laboratories has resulted in the stratification of patients into specific risk groups and thus several novel agents as well as targeted therapies have been introduced. Additionally, precision medicine will be applicable in the near future and thus the recent developments will facilitate the provision of safer modalities of therapy that may ultimately yield not only higher responses but also improved survival rates.This review represents a recent update on the role of various cytogenetic assays and molecular techniques in patients with acute lymphoblastic leukemia. It is composed of a number of sections including: history of cytogenetics, disease etiology and pathophysiology, utilization of various cytogenetic assays diagnostically, disease-specific cytogenetic and molecular abnormalities, common disease genetic subtypes, prognosis and risk stratification, refractory and relapsed disease, novel therapies, precision medicine and drug repurposing.

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Section: Molecular and Cytogenetic Abnormalities In All Patientsmentioning

confidence: 99%

Section: Prognosis and Risk Stratification In Allmentioning

confidence: 99%

Section: Drug Resistance and Relapse In All Patientsmentioning

confidence: 99%

Section: Prognosis and Risk Stratification In Allmentioning

confidence: 99%

See 2 more Smart Citations

Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

Wk¹,

Dridi²,

Ka³

2017

J Mol Genet Med

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“…Leukemia is a heterogeneous disease that comprises acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML). ALL accounts for 81% of childhood leukemia cases, while CLL and AML frequently occur in adults (7).…”

Section: Introductionmentioning

confidence: 99%

DNA methylation and leukemia susceptibility in China: Evidence from an updated meta-analysis

Jiang

Hong

et al. 2016

Molecular and Clinical Oncology

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Abstract. Mounting evidence supports a role for DNA methylation in the pathogenesis of leukemia; however, there no overview of these results in the Chinese population. The present study performed a comprehensive meta-analysis to establish candidate genes with an altered methylation status in Chinese leukemia patients. Eligible studies were identified through searching the National Center of Biotechnology Information PubMed and Wanfang databases. Studies were pooled and overall odds ratios with corresponding confidence intervals were calculated. A total of 4,325 leukemia patients and 2,010 controls from 94 studies on 53 genes were included in this meta-analysis, and 47 genes were found to be aberrantly methylated in leukemia patients. A further subgroup meta-analysis by leukemia subtype demonstrated that hypermethylation of 5 genes, namely cyclin-dependent kinase (CDKN)2A, DNA-binding protein inhibitor-4, CDKN2B, glioma pathogenesis-related protein 1 and p73, contributed to the risk of various subtypes of leukemia. In addition, a strong association between CDKN2A and leukemia was identified in Chinese (P<0.00001) but not in European patients. The aberrantly methylated genes identified in the present meta-analysis may help elucidate the mechanisms underlying the development of leukemia in Chinese patients.

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A novel and easy FxCycle™ violet based flow cytometric method for simultaneous assessment of DNA ploidy and six‐color immunophenotyping

et al. 2015

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Abnormal DNA ploidy is a valuable prognostic factor in many neoplasms, especially in hematological neoplasms like B-cell acute lymphoblastic leukemia (B-ALL) and multiple myeloma (MM). Current methods of flow-cytometric (FC) DNA-ploidy evaluation are either technically difficult or limited to three-to four-color immunophenotyping and hence, challenging to evaluate DNA-ploidy in minute tumor population with background rich of its normal counterpart cells and other hematopoietic cells. We standardized a novel sensitive and easy method of simultaneous evaluation of six-to sevencolor immunophenotyping and DNA-ploidy using a dye-FxCycle Violet (FCV). Linearity, resolution, and coefficient of variation (CV) for FCV were studied using chicken erythrocyte nuclei. Ploidy results of FCV were compared with Propidium iodide (PI) in 20 samples and intra-assay variation for FCV was studied. Using this six-color immunophenotyping & FCV-protocol DNA-ploidy was determined in bone-marrow samples from 124 B-ALL & 50 MM patients. Dilution experiment was also conducted to determine the sensitivity in detection of aneuploidy in minute tumor population. FCV revealed high linearity and resolution in 450/50 channel. On comparison with PI, CV of Go/G1-peak with FCV (mean-CV 4.1%) was slightly higher than PI (mean-CV 2.9%) but had complete agreement in ploidy results. Dilution experiment showed that aneuploidy could be accurately detected up to the limit of 0.01% tumor cells. Intraassay variation was very low with CV of 0.005%. In B-ALL, hypodiploidy was noted in 4%, hyperdiploidy in 24%, near-hyperdiploidy in 13% and remaining 59% were diploid. In MM, hypodiploidy was in 2%, hyperdiploidy in 58%, near-hyperdiploidy in 8% and remaining 30% were diploid. FCV-based DNA-ploidy method is a sensitive and easy method for simultaneous evaluation of six-color immunophenotyping and DNA analysis. It is useful in DNA-ploidy evaluation of minute tumor population in cases like minimal residual disease and MM precursor conditions. V C 2015 International Society for Advancement of CytometryKey terms DNA ploidy; cell cycle; FxCycle-violet; simultaneous multicolor immunophenotyping FLOW cytometric (FC) DNA content (DNA ploidy) evaluation is widely used tool in the prognostication of many solid tumors as well as hematological malignancies (1-5). It is an easy and rapid method to study the DNA content in the cells and to estimate proportion of cells present in different phases of the cell cycle. FC DNA ploidy analysis includes estimation of DNA index (DI) calculated by ratio of mean fluorescence of "G0/G1" peak of tumor cells to normal lymphocytes that reveals change in amount of DNA content of tumor cells in relation to normal diploid cells and percentage "S" phase provides an objective estimation of cell growth and may

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Childhood B-acute lymphoblastic leukemia: a genetic update

Cited by 111 publications

References 111 publications

Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

DNA methylation and leukemia susceptibility in China: Evidence from an updated meta-analysis

A novel and easy FxCycle™ violet based flow cytometric method for simultaneous assessment of DNA ploidy and six‐color immunophenotyping

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