Paucity of TEL‐AML 1 translocation, by multiplex RT‐PCR, in B‐lineage acute lymphoblastic leukemia (ALL) in Indian patients

Sazawal, Sudha; Bhatia, Kishor; Gutiérrez, Marina; Saxena, Renu; Arya, L. S.; Bhargava, Manorama

doi:10.1002/ajh.20000

Cited by 26 publications

(26 citation statements)

References 11 publications

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“…The 2 MLL-AF4-positive pediatric cases in the study were infants aged 7 and 9 months, respectively. This relatively low incidence and paucity of theE2A-PBX and MLL-AF4 transcripts in ALL cases is in accordance with results of earlier studies from our subcontinent [8,9]. The present pilot study is a prospective study that highlights the relative frequencies of the various common chimeric fusion transcripts in B-ALL cases in the Northern Indian population.…”

Section: Introductionsupporting

confidence: 77%

Incidence of Common Chimeric Fusion Transcripts in B-Cell Acute Lymphoblastic Leukemia: An Indian Perspective

et al. 2012

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Section: Introductionsupporting

confidence: 77%

Incidence of Common Chimeric Fusion Transcripts in B-Cell Acute Lymphoblastic Leukemia: An Indian Perspective

et al. 2012

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“…The frequency of BCR-ABL positivity in adults was 10/44 (22.7 %) and in pediatrics, 5/76 (6.5 %). This is in accordance with most of the studies reported from our subcontinent as well as few studies from the West [4][5][6][7][8][9][10][11][12]. Clinico-hematological features associated with BCR-ABL-positive ALL include high WBC count, older age, male predominance, and FAB L2 blast morphology.…”

Section: Discussionsupporting

confidence: 79%

“…Kantarjian et al [17] found the p190 type of breakpoint in 12 out of 24 adult ALL patients and the p210 in 11 patients, which is quiet comparable to the frequency noted in our study. In a study by Li Hui-yu et al [7], BCR-ABL positivity in ALL was 31.5 %, and all of their nine positive cases had p210 transcript.…”

Section: Discussionmentioning

confidence: 93%

Clinico-hematological, immunophenotyping, and molecular transcript profile of BCR–ABL-positive B cell acute lymphoblastic leukemias

et al. 2012

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The t(9;22) (BCR/ABL) and t(4;11) (AF4/MLL) positivity suggests a poor prognosis in B-acute lymphoblastic leukemia (ALL). Many western studies have highlighted the frequency and profile of BCR-ABL-positive B-ALL; however, data from the Indian subcontinent is limited. The aim of the pilot study is to present the complete clinicohematological, immunophenotyping, and molecular profile of BCR-ABL-positive B-ALL. It is a prospective study involving a total of 15 BCR-ABL-positive B-ALL cases diagnosed by bone marrow examination, immunophenotyping, and multiplex reverse transcriptase polymerase chain reaction assay in our institute. Out of the total 15 cases enrolled in the study, ten (67 %) were adult and five (33 %), pediatric. All cases had splenomegaly, hepatomegaly, high WBC count (>20×10 9 /L), and low platelet count (<100×10 9 /L) at presentation. Twelve of 15 (80 %) showed aberrant myeloid marker expression, of which 11 showed expression of two myeloid antigens (CD13 and CD117/33). The BCR-ABL transcript type in our study was p210 seen in 8/15 (53.3 %) cases, while p190 in 7/15 (46.6 %) cases. Thirteen of 15 (87 %) cases received imatinib in addition to the ALL induction regimen. Ten of 13 (77 %) of these had complete hematological remission at first check marrow. The disease-free interval, however, ranged from 4-6 months in 6/15 (40 %) cases. Analysis for BCR-ABL transcript is necessary in B-ALL as the cases may benefit from addition of imatinib to the treatment regimen.

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“…5,[21][22][23][24]. Initially, studies reported favorable outcome of t(12;21)-positive ALL patients compared with t(12;21)-negative ALL patients.…”

Section: Imaging Diagnosis Prognosismentioning

confidence: 99%

Expression Levels of TEL, AML1, and the Fusion Products TEL-AML1 and AML1-TEL versus Drug Sensitivity and Clinical Outcome in t(12;21)-Positive Pediatric Acute Lymphoblastic Leukemia

Stams

Boer

Beverloo

et al. 2005

Clinical Cancer Research

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Purpose: t(12;21)(p13; q22), present in f25% of pediatric precursor B-ALL, is highly sensitivity to L-asparaginase and the prognosis depends on the intensity of the treatment protocol. This study analyzes the relationship between the mRNA expression of the genes and fusion products involved in t(12;21), in vitro sensitivity to prednisolone, vincristine, and L-asparaginase, and longterm clinical outcome in t(12;21)+ acute lymphoblastic leukemia (ALL) patients. Experimental Design: Long-term clinical outcome in 45 t(12;21)+ ALL patients was related to mRNA expression of TEL, AML1, TEL-AML1, and AML1-TEL, determined by real-time quantitative PCR, and the in vitro sensitivity to prednisolone, vincristine, and L-asparaginase, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Results: A significant f3.5-fold lower TEL expression in t(12;21)+ compared with t(12;21)À ALL samples (P = 0.006) and normal controls (P = 0.004) was found. Expression of AML1 did not differ between t(12;21)+ and t(12;21)À ALL. However, AML1 expression in the leukemic cells was 2-fold higher compared with normal controls (P = 0.02). TheTEL-AML1 fusion product was expressed in all t(12;21)+ cases, whereas the reciprocal fusion product AML1-TEL was expressed in only 76%. High expression levels of TEL-AML1 [hazard ratio (HR), 1.3; 95% confidence interval (95% CI), 1.10-1.57; P = 0.003], AML1-TEL (HR, 4.9; 95% CI, 1.99-12.40; P = 0.001) and AML1 (HR, 1.1; 95% CI, 1.03-1.22; P = 0.006) were associated with a poor long-term clinical outcome within t(12;21)+ ALL. Cellular drug resistance towards prednisolone, vincristine, and L-asparaginase could not explain this predictive value. Multivariate analysis including age and WBC showed that only high AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL. Conclusion: High AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL.The t(12;21)(p13;q22) occurs in f25% of childhood acute lymphoblastic leukemia (ALL) and is restricted to precursor Bcell leukemia. The t(12;21) involves fusion of the TEL (ETV6) gene at 12p13 with the AML1 (CBFA2/RUNX1) gene at 21q22. The breakpoint most often occurs in intron 5 of TEL and intron 1 of AML1. A frequent translocation variant results in fusion between intron 5 of TEL and intron 2 of AML1. The TEL gene is a member of the ETS family of transcription factors and functions as a transcriptional repressor (1). AML1 encodes a transcription factor that acts as a transcription activator as well as a transcriptional repressor (2). Both genes are frequent targets of chromosomal translocations in a variety of myeloid and lymphoid leukemias (3, 4).Since the discovery of t(12;21), several studies addressed the prognostic value of this particular translocation (reviewed by Loh and Lubnitz; ref. 5). In general, t(12;21)-positive ALL is associated with a favorable prognosis although conflicting results have been reported (5). In the Dutch Childhood Oncology Group ALL-7 and ALL-8 treatment ...

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Paucity of TEL‐AML 1 translocation, by multiplex RT‐PCR, in B‐lineage acute lymphoblastic leukemia (ALL) in Indian patients

Cited by 26 publications

References 11 publications

Incidence of Common Chimeric Fusion Transcripts in B-Cell Acute Lymphoblastic Leukemia: An Indian Perspective

Incidence of Common Chimeric Fusion Transcripts in B-Cell Acute Lymphoblastic Leukemia: An Indian Perspective

Clinico-hematological, immunophenotyping, and molecular transcript profile of BCR–ABL-positive B cell acute lymphoblastic leukemias

Expression Levels of TEL, AML1, and the Fusion Products TEL-AML1 and AML1-TEL versus Drug Sensitivity and Clinical Outcome in t(12;21)-Positive Pediatric Acute Lymphoblastic Leukemia

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