Abnormalities of Chromosomes 8, 11, 14, and X in T-Prolymphocytic Leukemia Studied by Fluorescence In Situ Hybridization

Maljaei, Seyed Hoda; Brito‐Babapulle, Vasantha; Hiorns, Lynne R.; Catovsky, Daniel

doi:10.1016/s0165-4608(97)00410-x

Cited by 92 publications

(74 citation statements)

References 16 publications

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“…Th e most common characteristic chromosome abnormality, seen in 80% of cases, is inversion of chromosome 14 with breakpoints in the long arm at q11 and q32 (inv (14)(q11;q32)). Reciprocal tandem translocations between the two chromosomes 14 occur in 10% (t14;14)(q11;q32) (17,18). Th ese two rearrangements involve the 14q11 and 14q32.1 loci, where the genes coding for TCRα and the protooncogene TCL-1 are localized, respectively.…”

Section: Discussionmentioning

confidence: 99%

T-Cell Prolymphocytic Leukemia

Graham

Cooper²,

Krause³

2013

Baylor University Medical Center Proceedings

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Section: Discussionmentioning

confidence: 99%

T-Cell Prolymphocytic Leukemia

Graham

Cooper²,

Krause³

2013

Baylor University Medical Center Proceedings

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“…64 Although Tcl1 was not identified in these screens, it is possible that MYC and TCL1 form yet another set of complementing genes. This suggestion gains weight from the observation that MYC is overexpressed in human T-cell lymphomas bearing TCL1 translocations 20,65 and could be tested by crossing transgenics in which both MYC and TCL1 are targeted to the B-cell lineage.…”

Section: Discussionmentioning

confidence: 99%

“…In mature human T-cell lymphomas that have frequent TCL1 rearrangements, abnormalities of Chr 8, which contains MYC at 8q24, are observed in 70% to 80% of cases, but the nature of the specific complementing genes required for transformation has not been defined. 20,21 For some human B-cell lymphomas with elevated TCL1 levels, such as BL, heightened expression of MYC caused by specific activating translocations is frequently observed in altered gene expression profiles. 22 In the present study, we have used this TCL1-tg lymphoma model to examine how TCL1 alters GC-related functions that may contribute to B-cell transformation and to determine whether genome instability and/or altered MYC expression may complement TCL1 dysregulation in mature B-cell lymphomas.…”

Section: Introductionmentioning

confidence: 99%

Dysregulated TCL1 requires the germinal center and genome instability for mature B-cell transformation

Shen

Ferguson

Renard

et al. 2006

Blood

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IntroductionMost common B-cell lineage lymphomas in humans originate by transformation of germinal center (GC) B cells. These include classes of non-Hodgkin lymphoma (NHL) designated follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL) as well as classical Hodgkin lymphoma. 1 FL and BL are characterized by recurring reciprocal chromosome (Chr) translocations that fuse Ig genes either with the BCL2 cell survival gene or with the MYC proto-oncogene, respectively. 2,3 Also, reciprocal Chr translocations involving the BCL6 transcriptional repressor gene and more than 20 partner loci, including the Ig genes, typify DLBCL. 4 These and additional tumor-promoting genes are subsequently expressed under the control of Ig regulatory sequences rather than their native regulatory elements, resulting in dysregulated expression. Interestingly, MYC, BCL6, and other genes, such as TCL1, are also expressed at high levels in many NHLs in the absence of activating translocations. In these cases, inappropriately high expression is a consequence of other genetic or possibly epigenetic alterations and is likely contributory to the transformation process. [5][6][7] The TCL1 proto-oncogene encodes a 14-kDa intracellular protein that associates in a multimeric complex with the serine/ threonine kinase AKT. [7][8][9][10][11] Interactions with TCL1 enhance AKT activation and, by an unknown mechanism, TCL1 stimulates the protein kinase C-mitogen-activated protein kinase-extracellular signal-related kinase (PKC-MAPK-ERK) signal transduction pathway, promoting cell survival and proliferation. 8,12,13 In human T cells, TCL1 is normally expressed only by immature cortical thymocytes and by activated peripheral T cells. 13,14 However, dysregulated expression from Chr rearrangements between TCL1 and T-cell receptor (TCR) loci results in persistent high-level expression in mature T-cell leukemia/lymphomas. 15 A direct, initiating role for heightened TCL1 expression in T-cell transformation is suggested by studies of transgenic mice with T-cell lineage-restricted TCL1 expression that develop mature T-cell leukemias following an extended premalignant phase of polyclonal expansion. 16 Despite its original identification in T-cell leukemias, TCL1 seems to have an even more prominent role in B cells and is For personal use only. on May 11, 2018. by guest www.bloodjournal.org From differentially expressed during normal B-cell maturation. Expression is robust from pre-B through follicular B-cell development, but is down-regulated during the GC reaction and is silenced in post-GC memory B and plasma cells. 17 High levels of TCL1 expression have been documented for human B-cell lymphomas originating from pre-GC and GC B cells and in AIDS-related lymphomas of post-GC cell origin. [17][18][19] The suggestion that inappropriately high expression in the GC could contribute to GC B-cell lymphomagenesis is strongly supported by studies of mice bearing a pE-B29-TCL1 transgene expressed in both T and B cells, which develop mat...

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“…14 Trisomy 8 or iso8q is seen in up to two-thirds of cases ( Figure 4A). 15 The C-MYC localized at 8q24 is not rearranged in these cases, but the encoded protein may be overexpressed. Although 11q23 abnormalities are rarely detected on cytogenetics, molecular analysis frequently detects abnormalities of the ATM gene.…”

Section: Making An Accurate Diagnosismentioning

confidence: 99%

“…Nevertheless, our experience suggests that consolidation with an HSCT in first or subsequent remission offers potential advantages to patients. We have recently reviewed data on 28 T-PLL patients treated on a common protocol with alemtuzumab followed by either autologous (15) or allogeneic (13) transplantation (Table 4). 31 We compared clinical outcomes to 23 retrospectively selected patients who had achieved a CR after alemtuzumab treatment and survived at least 6 months but had not undergone a transplant (non-HSCT group).…”

Section: Who Should Have An Hsctmentioning

confidence: 99%