BCR-ABL, ETV6-RUNX1 and E2A-PBX1: Prevalence of the most common acute lymphoblastic leukemia fusion genes in Mexican patients

Jiménez-Morales, Silvia; Miranda-Peralta, Enrique; Saldaña-Álvarez, Yolanda; Pérez-Vera, Patricia; Paredes‐Aguilera, Rogelio; Rivera-Luna, Roberto; Velázquez‐Cruz, Rafael; Ramírez‐Bello, Julián; Carnevale, Alessandra; Orozco, Lorena

doi:10.1016/j.leukres.2008.03.021

Cited by 34 publications

(35 citation statements)

References 31 publications

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“…The frequency of patients with the TEL/AML1 fusion gene was 17.1%, demonstrating that this is the most common genetic defect in Serbian children with ALL, as in many other populations [18,19]. Biological and clinical characteristics and therapy response of TEL/AML1 positive patients were also similar to other reports [20].…”

Section: Discussionsupporting

confidence: 83%

“…Significantly higher incidence of BCR/ABL was found in Indian [9], as well as in Pakistani population [10]. In Mexican population, high prevalence of E2A/PBX1 positive ALL was reported [19], while Spanish authors published unusually low prevalence of TEL/AML1 [25]. This is the first molecular study of the presence and clinical features of specific fusion genes and their impact on treatment response in Serbian children with ALL.…”

Section: Discussionmentioning

confidence: 78%

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Clinical features of the most common fusion genes in childhood acute lymphoblastic leukemia

Lazić

Tos̆ić²,

Dokmanović

et al. 2009

Med Oncol

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Contemporary protocols ensure high-remission rate and long-term free survival in children with acute lymphoblastic leukemia (ALL), but small percentage of patients is still incurable. Molecular genetic methods helped to establish submicroscopic classification as well as minimal residual disease follow-up, considered to be responsible for relapse. Our study enrolled 70 pediatric patients with de novo ALL, analyzed using reverse transcriptase-polymerase chain reaction for the presence of four major risk-stratifying translocations (BCR/ABL, MLL/AF4, TEL/AML1, and E2A/PBX1). Bone marrow samples were collected at diagnosis, at the end of induction phase, and after intensive chemotherapy with the aim to establish the correlation between chromosomal aberration, clinical features, and treatment response. Presenting the results of this study, we offer another evidence of variable incidence and clinical characteristics of ALL subtypes.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 78%

Clinical features of the most common fusion genes in childhood acute lymphoblastic leukemia

Lazić

Tos̆ić²,

Dokmanović

et al. 2009

Med Oncol

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“…The E2A-PBX1 translocation seen more frequently in nonCaucasians constitute 5-6% of translocations seen in childhood ALL and 3% of adult ALL (Crist et al 1990;Faderl et al 1998). In a study of Mexican patients, 6 of 52 (11.5%) childhood ALL patients expressed the E2A-PBX1 fusion gene transcript that shows a high prevalence of that fusion gene compared to other populations (Jiménez-Morales et al 2008). All the four patients showing E2A-PBX1 fusion gene in the present study were males.…”

Section: Discussionsupporting

confidence: 44%

RT-PCR and real-time PCR analysis of E2A-PBX1, TEL-AML1, mBCR-ABL and MLL-AF4 fusion gene transcripts in de novo B-lineage acute lymphoblastic leukaemia patients in south India

Natarajan

Rajalekshmy

Rajkumar

et al. 2011

J Genet

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“…21 Given the importance of E2A in lymphoid differentiation, it is perhaps not surprising that in 4%-12% of pediatric acute lymphoblastic leukemia cases, regions of the E2A and PBX1 genes are fused by a chromosomal translocation between chromosomes 1 and 19 [t(1; 19)(q23;p13.3)]. 22,23 These leukemias predominantly show a pre-B cell immunophenotype 24 and are associated with expression of the proto-oncogene product E2A-PBX1. 25 This chimeric protein includes a large N-terminal region of E2A containing both AD1 and AD2 fused with most of PBX1, including its C-terminal DNAbinding homeodomain.…”

Section: Introductionmentioning

confidence: 99%

Structural basis of CBP/p300 recruitment in leukemia induction by E2A-PBX1

Denis

Chitayat

Plevin

et al. 2012

Blood

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E-proteins are critical transcription factors in B-cell lymphopoiesis. E2A, 1 of 3 E-protein–encoding genes, is implicated in the induction of acute lymphoblastic leukemia through its involvement in the chromosomal translocation 1;19 and consequent expression of the E2A-PBX1 oncoprotein. An interaction involving a region within the N-terminal transcriptional activation domain of E2A-PBX1, termed the PCET motif, which has previously been implicated in E-protein silencing, and the KIX domain of the transcriptional coactivator CBP/p300, critical for leukemogenesis. However, the structural details of this interaction remain unknown. Here we report the structure of a 1:1 complex between PCET motif peptide and the KIX domain. Residues throughout the helical PCET motif that contact the KIX domain are important for both binding KIX and bone marrow immortalization by E2A-PBX1. These results provide molecular insights into E-protein–driven differentiation of B-cells and the mechanism of E-protein silencing, and reveal the PCET/KIX interaction as a therapeutic target for E2A-PBX1–induced leukemia.

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BCR-ABL, ETV6-RUNX1 and E2A-PBX1: Prevalence of the most common acute lymphoblastic leukemia fusion genes in Mexican patients

Cited by 34 publications

References 31 publications

Clinical features of the most common fusion genes in childhood acute lymphoblastic leukemia

Clinical features of the most common fusion genes in childhood acute lymphoblastic leukemia

RT-PCR and real-time PCR analysis of E2A-PBX1, TEL-AML1, mBCR-ABL and MLL-AF4 fusion gene transcripts in de novo B-lineage acute lymphoblastic leukaemia patients in south India

Structural basis of CBP/p300 recruitment in leukemia induction by E2A-PBX1

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