Identification of two subgroups of mantle cell leukemia with distinct clinical and biological features

Vizcarra, E; Martínez-Climent, José A.; Benet, Isabel; Marugán, Isabel; Terol, María José; Prósper, Felipe; Marco, J; Sanchez, Dolors; Ferrández, Antonio; Tormo, Mar; Sarsotti, Elena; Ferrer, Rosa; García, M Reynoso; Ortuño, Francisco José; Montagud, Mario; Garcı́a-Conde, J

doi:10.1038/sj.thj.6200111

Cited by 16 publications

(12 citation statements)

References 24 publications

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“…4d). Nevertheless, specific genomic changes associated with leukemic dissemination and shorter survival times have been observed previously [63,64]. The TF IRF-4 known to separate DLBCL-nonGC from DLBCL-GC [57] and to be expressed in a variety of lymphomas of mature B cells research article American Journal of Hematology(CLL, MM, DLBCL-nonGC) [57,65,66] here show an high mRNA expression in MCL.…”

Section: Discussionmentioning

confidence: 92%

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

et al. 2010

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Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment. Am. J. Hematol. 85:418-425, 2010. V

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Section: Discussionmentioning

confidence: 92%

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

et al. 2010

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“…In MCL, ZAP-70 tends to be negative 18,28 and CD38 is expressed in more than half of the cases, although their prognostic value is not clear. 19,20,29,30 In SMZL, CD38 is expressed in about half of the cases 22,31 and in a recent report it appears to correlate with unmutated IgVH and aggressive clinical behavior. 31 Our series is too small to firmly demonstrate if these markers have a prognostic impact.…”

Section: Discussionmentioning

confidence: 99%

IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL)

et al. 2006

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B-prolymphocytic leukemia (B-PLL) is a rare disease with poor prognosis. To further characterize the biological features of this disease, we analyzed immunoglobulin heavy chain (IgVH) mutations, ZAP-70 and CD38 in 19 cases with de novo B-PLL. Immunoglobulin heavy chain genes analysis showed an unmutated pattern (498% homology to germ line) in 9/17 cases (53%), with 100% homology in eight. In the remaining, it ranged from 90 to 97.4%, with three cases slightly mutated (98-95%) and five heavily mutated (o95%). All B-PLL utilized members of VH3 (11/17) and VH4 (6/17) families, with V3-23, V4-59 and V4-34 gene accounting for more than half of them, regardless of mutational status. ZAP-70, assessed by flow cytometry, ranged from 1 to 91% cells, being X20% in 57% of cases. CD38 ranged from 1 to 99% (median 21%). There was no correlation between IgVH status and ZAP-70 or CD38 expression, but male gender and del(17p) were more common in the unmutated group. Neither IgVH mutations, CD38 expression nor del(17p) influenced patients' outcome. Unexpectedly, ZAP-70 þ B-PLL patients survived longer (40 months) than ZAP-70À B-PLL (8 months). B-PLL appears biologically heterogeneous regarding IgVH mutations, ZAP-70 and CD38 expression, showing a pattern distinct from that of other lymphoproliferative disorders.

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“…These specific subgroups of patients should be followed clinically and analysed with other biological makers in more detail in order to clarify whether they are closer related to CLL or mantle cell lymphoma or follicular lymphoma, respectively. Vizcarra et al 44 provided already first evidence that a specific subtype of B-lymphoproliferative disease exists, which shows a t(11;14)(q13;q32)/IgH-CCND1 rearrangement with a clinical presentation indistinguishable from CLL and is characterized by gains of 3q, 8q and 15q as well as loss of 6q, 9p, 13q and 17p. All these imbalances with exception of 9p loss were also detected in our cohort of CLL patients with t (11;14).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping

et al. 2007

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In CLL data from chromosome banding analysis (CBA) have been scarce due to the low proliferative activity of CLL cells in vitro. We improved the cultivation technique using an immunostimulatory CpG-oligonucleotide DSP30 and IL-2. A total of 506 CLL samples were analysed with CBA and interphase FISH using probes for the detection of trisomy 12, IgH rearrangements and deletions of 6q21, 11q22.3 (ATM), 13q14 (D13S25 and D13S319) and 17p13 (TP53). A total of 500 of 506 (98.8%) cases were successfully stimulated for metaphase generation and are subject to this study. Aberrations were detected in 415 of 500 (83.0%) cases by CBA and in 392 of 500 (78.4%) cases by FISH. CBA detected 832 abnormalities and FISH only 502. Therefore, CBA offers important information in addition to FISH. (1) CLL is characterized mainly by genomic imbalances and reciprocal translocations are rare. (2) A subgroup with complex aberrant karyotype (16.4%) is identified which is associated with an unmutated IgV H status and CD38 expression (P ¼ 0.034 and 0.02, respectively). (3) Additional abnormalities are detectable providing new biological insights into different CLL subclasses revealing a much more heterogeneous pattern of cytogenetic abnormalities as assumed so far based on FISH data only. Therefore, prospective clinical trials should evaluate the prognostic impact of newly available CBA data.

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Identification of two subgroups of mantle cell leukemia with distinct clinical and biological features

Cited by 16 publications

References 24 publications

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL)

Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping

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