Chromosomal translocations involving the IGH@ locus in B-cell precursor acute lymphoblastic leukemia: 29 new cases and a review of the literature

Chapiro, Élise; Radford‐Weiss, Isabelle; Cung, Hong-Anh; Dastugue, Nicole; Nadal, Nathalie; Taviaux, Sylvie; Barin, Carole; Struski, Stéphanie; Talmant, Pascaline; Vandenberghe, Peter; Mozziconacci, Marie‐Joëlle; Tigaud, Isabelle; Lefebvre, Catherine Lemieux; Penther, Dominique; Bastard, Christian; Lippert, Éric; Mugneret, Francine; Romana, Serge; Bernard, Olivier A.; Harrison, Christine J.; Russell, Lisa J.; Nguyen‐Khac, Florence

doi:10.1016/j.cancergen.2013.04.004

Cited by 26 publications

(17 citation statements)

References 43 publications

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“…It was difficult to recognize the true incidence of cases of de novo acute B-ALL with MYC and BCL-2 rearrangements, and the reported cases so far are probably still overestimated as most of documented cases within this category either represent high-grade B-cell neoplasm with DH rearrangements and blastoid morphology but with mature phenotype [6,7] which are currently classified as high-grade B-cell neoplasm with MYC and BCL-2 gene rearrangements [1] or cases of Burkitt leukemia/lymphoma (with L3 morphology [8]) or cases with blastic transformation on top FL [9,10].…”

Section: Discussionmentioning

confidence: 99%

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De Novo Precursor B-Lymphoblastic Leukemia/Lymphoma With Double-Hit Gene Rearrangements (MYC/BCL-2) Presented With Spinal Cord Compression and Acquired Factor XIII Deficiency

et al. 2017

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Double-hit lymphomas (DHLs) are aggressive mature B-cell neoplasms associated with rearrangements involving MYC and B-cell lymphoma-2 (BCL-2). Such DH events are extremely rare in Bcell precursor acute lymphoblastic leukemia (B-ALL), especially in young adults. A 29-year-old male patient initially presented to emergency department with right mandibular mass of 2 months duration associated with intermittent fever. Laboratory workup revealed very high lactate dehydrogenase at 2,026.0 U/L. Peripheral blood revealed pancytopenia with many circulating blasts (about 77%). Bone marrow (BM) aspirate revealed infiltration with many small sized blasts of very high nucleocytoplasmic ratio, finely dispersed nuclear chromatin and prominent nucleoli. The BM biopsy reflected marked hypercellularity with diffuse replacement by sheets of blasts, positive for TdT, PAX-5, CD10, cMYC, BCL-2 and CD20 with Ki-67 > 90%. Flow cytometry on BM revealed a precursor B-immunophenotype (CD45 (dim), CD19, CD10, Tdt and CD20). The blasts are negative for cytoplasmic and surface IgM. Cytogenetics revealed complex karyotype: 46,XY,del(6)(q21q23),t(8;22)(q24.1;q11.2),t(14;18)(q32;q21)(20). A diagnosis of B-lymphoblastic leukemia/lymphoma with t(8;22) (q24.1;q11.2) and t(14;18)(q32;q21) was made. Fluorescent in situ hybridization (FISH) analysis revealed an abnormal hybridization signal pattern for CDKN2A probe, indicating biallelic (homozygous) deletion of the short arm of chromosome 9 (9p) in 94% of the cells analyzed. The patient had severe life-threatening bleeding despite of normal prothrombin time (PT) and activated partial thromboplastin time (APTT) due to acquired factor XIII deficiency, an overlooked rare coagulopathy disorder. In addition, the patient developed acute sudden onset paraplegia, and magnetic resonance imaging (MRI) of spine showed acute cord compression which necessitated emergency radiotherapy after which chemotherapy was started on hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone) protocol. MRI showed dramatic resolution of the mass. Very few cases of B-ALL with DH rearrangement with true precursor B-cell phenotype (positivity for TdT with negativity for surface light chain) have been reported. Many of these had frequent central nervous system (CNS) involvement, with complex karyotypes, highly aggressive course, with short survival of less than 1 year. This case however showed very good response to treatment. In contrary to DHL, de novo B-ALL with double-hit rearrangements is more prevalent in pediatrics and young adults. Although most of reported cases represent transformation of follicular lymphoma, our patient's young age, acute onset and absent lymphadenopathies all support de novo ALL.

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Section: Discussionmentioning

confidence: 99%

“…Cases with a well-documented true immature immunophenotype, positive for TdT and negative for surface light chains, are rare [4][5][6][7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

De Novo Precursor B-Lymphoblastic Leukemia/Lymphoma With Double-Hit Gene Rearrangements (MYC/BCL-2) Presented With Spinal Cord Compression and Acquired Factor XIII Deficiency

et al. 2017

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“…Several partners of IGH in BCP-ALL have been identified, including inhibitor of DNA binding 4 (ID4) at 6p22 [137], EPOR at 19p13 [98,138,139], a member of the CCAAT/enhancer binding protein (CEBP) family (e.g. CEBPA, CEBPG, CEBPB, CEBPD, CEBPE) [140,141] , BCL2 [142], the LIM domain Homeobox 4 (LHX4) at 1q25, and rarely, Interleukin 3 (IL-3) at 5q31 [136]. However, the most common IGH partner is CRLF2, also known as thymic stromal-derived lymphopoietin (TSLP) receptor located at the pseudoautosomal region 1 (PAR1) of Xp22.3/Yp11.3 [124].…”

Section: Igh-rearranged Allmentioning

confidence: 99%

Molecular basis and clinical significance of genetic aberrations in B-cell precursor acute lymphoblastic leukemia

Ghazavi

Lammens

Roy

et al. 2015

Experimental Hematology

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“…These translocations are recurrent but are rare in B-ALL, occurring in less than 5% of cases [22]. Five members of the CEBP gene family have been shown to undergo translocation with the IGH locus [23]. IGH translocations are prevalent in teenagers and young adults with ALL and are associated with a poor outcome [24].…”

Section: A) Primary Chromosomal Abnormalities (I) Chromosomal Translomentioning

confidence: 99%

Routine Cytogenetic Analysis of Chromosome Abnormalities in Acute Lymphoblastic Leukemia

Meng¹

2015

Int Jour of Biomed Res

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Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Acquired chromosomal and genetic abnormalities have been used to define distinct biological and clinical subtypes of ALL. These aberrations have been shown to be associated with patient outcome and are used to direct therapy. Conventional cytogenetics analysis (CCA) is currently the gold standard to detect chromosome abnormalities in hematological malignancies. In this review we briefly describe the CCA methodology, advantages and limitations of CCA, the main chromosomal abnormalities and their prognostic significance in ALL.

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Chromosomal translocations involving the IGH@ locus in B-cell precursor acute lymphoblastic leukemia: 29 new cases and a review of the literature

Cited by 26 publications

References 43 publications

De Novo Precursor B-Lymphoblastic Leukemia/Lymphoma With Double-Hit Gene Rearrangements (MYC/BCL-2) Presented With Spinal Cord Compression and Acquired Factor XIII Deficiency

De Novo Precursor B-Lymphoblastic Leukemia/Lymphoma With Double-Hit Gene Rearrangements (MYC/BCL-2) Presented With Spinal Cord Compression and Acquired Factor XIII Deficiency

Molecular basis and clinical significance of genetic aberrations in B-cell precursor acute lymphoblastic leukemia

Routine Cytogenetic Analysis of Chromosome Abnormalities in Acute Lymphoblastic Leukemia

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