Frequency of 5′IGH deletions in B-cell chronic lymphocytic leukemia

Quintero‐Rivera, Fabiola; Nooraie, Farzad; Rao, P. Nagesh

doi:10.1016/j.cancergencyto.2008.12.004

Cited by 22 publications

(24 citation statements)

References 30 publications

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“…These include a cryptic deletion on 8q24.1 including MYC [6,8], gain of an extra copy of MYC (+MYC ) [4,5,29], or deletion of IGH@, usually 5’ [3,4,6,30,31]. Although a deletion of the MYC -specific signal on der 8q24.1 locus was also observed in our patient using IGH-MYC fusion probe (1Y2G1R), it is not identical to the reported deletion by Reddy et al in 2006 [6,8].…”

Section: Discussionmentioning

confidence: 99%

“…with no IGH@ deletion by FISH [30]. It is still unclear whether this microdeletion is a polymorphic feature of this locus and represents a region of frequent mutation and recombination, or it exhibits some susceptibility risks for CLL [3,24,31,41]. …”

Section: Discussionmentioning

confidence: 99%

“…Immunophenotypically, aberrant expression of CD5, CD20, CD22, CD23, CD38, CD43 and CD79 is diagnostic or prognostic of B-cells in CLL [2]. Common cytogenetic anomalies include deletion of 13q14.3 (most frequent) and/or 13q34, deletion of 11q, deletion of 17p, trisomy 12 and IGH@ rearrangement [3]. …”

Section: Introductionmentioning

confidence: 99%

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Atypical rearrangement involving 3′-IGH@ and a breakpoint at least 400 Kb upstream of an intact MYC in a CLL patient with an apparently balanced t(8;14)(q24.1;q32) and negative MYC expression

et al. 2013

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The t(8;14)(q24.1;q32), the cytogenetic hallmark of Burkitt’s lymphoma, is also found, but rarely, in cases of chronic lymphocytic leukemia (CLL). Such translocation typically results in a MYC-IGH@ fusion subsequently deregulating and overexpressing MYC on der 14q32. In CLL, atypical rearrangements resulting in its gain or loss, within or outside of IGH@ or MYC locus, have been reported, but their clinical significance remains uncertain. Herein, we report a 67 year-old male with complex cytogenetic findings of apparently balanced t(8;14) and unreported complex rearrangements of IGH@ and MYC loci. His clinical, morphological and immunophenotypic features were consistent with the diagnosis of CLL.Interphase FISH studies revealed deletions of 11q22.3 and 13q14.3, and an extra copy of IGH@, indicative of rearrangement. Karyotype analysis showed an apparently balanced t(8;14)(q24.1;q32). Sequential GPG-metaphase FISH studies revealed abnormal signal patterns: rearrangement of IGH break apart probe with the 5’-IGH@ on derivative 8q24.1 and the 3’-IGH@ retained on der 14q; absence of MYC break apart-specific signal on der 8q; and, the presence of unsplit 5’-MYC-3’ break apart probe signals on der 14q. The breakpoint on 8q24.1 was found to be at least 400 Kb upstream of 5’ of MYC. In addition, FISH studies revealed two abnormal clones; one with 13q14.3 deletion, and the other, with concurrent 11q deletion and atypical rearrangements. Chromosome microarray analysis (CMA) detected a 7.1 Mb deletion on 11q22.3-q23.3 including ATM, a finding consistent with FISH results. While no significant copy number gain or loss observed on chromosomes 8, 12 and 13, a 455 Kb microdeletion of uncertain clinical significance was detected on 14q32.33. Immunohistochemistry showed co-expression of CD19, CD5, and CD23, positive ZAP-70 expression and absence of MYC expression. Overall findings reveal an apparently balanced t(8;14) and atypical complex rearrangements involving 3’-IGH@ and a breakpoint at least 400 Kb upstream of MYC, resulting in the relocation of the intact 5’-MYC-3’ from der 8q, and apposition to 3’-IGH@ at der 14q. This case report provides unique and additional cytogenetic data that may be of clinical significance in such a rare finding in CLL. It also highlights the utility of conventional and sequential metaphase FISH in understanding complex chromosome anomalies and their association with other clinical findings in patients with CLL. To the best of our knowledge, this is the first CLL reported case with such an atypical rearrangement in a patient with a negative MYC expression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Atypical rearrangement involving 3′-IGH@ and a breakpoint at least 400 Kb upstream of an intact MYC in a CLL patient with an apparently balanced t(8;14)(q24.1;q32) and negative MYC expression

et al. 2013

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“…Recent improvements in cell culture techniques due to the addition of B cell mitogens such as pokeweed mitogen and CpG-oligonucleotide, with or without interleukin-2 (IL-2), have increased the detection rate of chromosomal aberrations [51,[62][63][64]. These modifications have resulted in the detection of translocations in approximately 20% of CLL cases [51], and indicated that patients with translocations have a poorer prognosis [63].…”

Section: Translocations In Cllmentioning

confidence: 98%

New insights into the pathobiology of chronic lymphocytic leukemia

Gunnarsson

Rosenquist

2011

J Hematopathol

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Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a varying clinical outcome; however, the pathogenic mechanisms involved in disease development have remained largely unknown. In recent years, novel biomarkers, such as certain recurrent genomic alterations and the immunoglobulin heavy variable gene mutational status, have significantly improved the subdivision of the disease along with the prognostic assessment of individual patients. Advanced molecular studies have also revealed important genetic/epigenetic events and potential susceptibility loci for CLL, as well as implicating antigens in CLL development. Furthermore, the presence of monoclonal B cell lymphocytosis (MBL) has been demonstrated to precede CLL and appears to be a pre-leukemic condition. In this review, we will not only focus on recent developments made in the fields of genetics and immunogenetics in CLL, but also provide a brief overview of MBL, since we believe that advancements in these areas will have a major impact on our understanding of CLL pathobiology.

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“…6 About 80% of cases of CLL/SLL have FISH detectable cytogenetic abnormalities, and, of these, 13q14 deletion suggests a favourable prognosis, while trisomy 12, 11q22e23 deletion (targeting the ATM gene) and 17p13 deletion (targeting the p53 gene), predict a poor outcome. 7,8 Morphological differential diagnoses 1 Reactive lymphoid hyperplasia lacks the monomorphous diffuse effacement of nodal architecture and proliferation centres of CLL/SLL. CD5 expression by B cells is restricted to mantle zones in hyperplastic nodes.…”

Section: Pre-germinal Centre Lymphomamentioning

confidence: 99%