Gene-expression profiling of Waldenström macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma

Chng, Wee Joo; Schop, Roelandt F.J.; Price-Troska, Tammy; Ghobrial, Irène M.; Kay, Neil E.; Jelinek, Diane F.; Gertz, Morie A.; Dispenzieri, Angela; Lacy, Martha Q.; Kyle, Robert A.; Greipp, Philip R.; Tschumper, Renee C.; Fonseca, Rafaël; Bergsagel, P. Leif

doi:10.1182/blood-2006-02-005488

Cited by 162 publications

(147 citation statements)

References 39 publications

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“…Interestingly, one of the upregulated genes in WM-BL was IL6. This finding is consistent with the recent report by Chng et al 7 and previous data showing high serum IL6 concentrations in patients with WM. 30 Two of the genes (IL4R and BACH2) downregulated in WM-BL compared with CLL-BL and normal BL have important functions in B-cell development.…”

Section: Resultssupporting

confidence: 83%

“…The expression profile of WM using the entire malignant population (CD19 þ and CD138 þ cells) has recently been published. 7 In our study, the separate isolation of CD19 þ B cells and CD138 þ PC gave us the opportunity to search for the expression profile that defined clonal BL of WM (WM-BL) with relation to NBL and the molecular fingerprint of clonal PC of WM (WM-PC) with respect to NPC. The comparative analyses of the gene expression profile of WM-BL vs NBL identified a set of 171 genes differentially expressed between the two groups (109 genes were downregulated in WM-BL and 62 were upregulated).…”

Section: Resultsmentioning

confidence: 99%

“…The only recurrent chromosomal abnormality identified by conventional cytogenetics and FISH studies is deletion of 6q. 6 The differences between clonal cell compartments of WM and their cell counterpart in other lymphoproliferative disorders have not yet been sufficiently explored 7 abstract No. 503) mainly because of the difficulty in selecting pure clonal cell populations in sufficient amounts to apply genetic analysis.…”

Section: Introductionmentioning

confidence: 99%

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Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

et al. 2007

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The tumoral clone of Waldenströ m's macroglobulinemia (WM) shows a wide morphological heterogeneity, which ranges from B lymphocytes (BL) to plasma cells (PC). By means of genomewide expression profiling we have been able to identify genes exclusively deregulated in BL and PC from WM, but with a similar expression pattern in their corresponding cell counterparts from chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), as well as normal individuals. The differentially expressed genes have important functions in B-cell differentiation and oncogenesis. Thus, two of the genes downregulated in WM-BL were IL4R, which plays a relevant role in CLL B-cell survival, and BACH2, which participates in the development of class-switched PC. Interestingly, one of the upregulated genes in WM-BL was IL6. A set of four genes was able to discriminate clonal BL from WM and CLL: LEF1 (WNT/b-catenin pathway), MARCKS, ATXN1 and FMOD. We also found deregulation of genes involved in plasma cell differentiation such as PAX5, which was overexpressed in WM-PC, and IRF4 and BLIMP1, which were underexpressed. In addition, three of the target genes activated by PAX5 -CD79, BLNK and SYK -were upregulated in WM-PC. In summary, these results indicate that both PC and BL from WM are genetically different from the MM and CLL cell counterpart.

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Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

et al. 2007

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“…Genes involved in the MAPK pathway are elevated in WM patients [24]. Recent studies also indicated that protein kinase C beta (PKC□) is upregulated in WM [25].…”

Section: Cddo-im Targets Survival Pathways In Wmmentioning

confidence: 99%

CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenström macroglobulinemia

et al. 2008

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Waldenström macroglobulinemia (WM) is a B-cell malignancy that remains incurable. Synthetic triterpenoids (ST), 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), its methyl ester derivative (CDDO-Me) and imidazolide derivative (CDDO-Im) induce cell death and inhibit growth of various malignancies and hold promise as treatment for cancer patients. We examined the therapeutic potential of these compounds in WM. All three forms of CDDO induced equal toxicity in BCWM.1 cells. In malignant B cells from WM patients, CDDO-Im induced the greatest toxicity. CDDO-Im inhibited proliferation at nanomolar concentrations and arrested the cells in G0/G1. CDDO-Im induced apoptotic cell death that was partially abolished in the presence of caspase inhibitor. CDDO-Im also inhibited survival pathways that have been shown to be important in WM. Overall, our data suggest that ST are likely to provide therapeutic efficacy for WM patients.

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“…25 The value of stem cell transplant for chronic lymphatic leukemia is well documented. 26,27 Waldenströ m macroglobulinemia lacks the typical adverse cytogenetics 28 that are associated with diseases in which autologous stem cell transplant is regularly contemplated such as multiple myeloma.…”

Section: Why Consider a Transplant In This Disease?mentioning

confidence: 99%

Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique

Gertz

Reeder

Kyle

et al. 2011

Bone Marrow Transplant

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Waldenströ m macroglobulinemia is a highly chemosensitive lymphoplasmacytic lymphoma with response rates of 90% to firstline chemotherapy. The fraction of patients undergoing stem cell transplant for this disorder appears to be lower than that of patients with multiple myeloma. The indolent nature and favorable genetic profile should make Waldenströ m an ideal disorder for autologous stem cell transplant, with high response rates that are durable. We review the literature on autologous and allogeneic transplants for Waldenströ m macroglobulinemia and conclude that autologous transplant is effective and underutilized in the management of this disorder. Allogeneic transplant should be considered investigational and used only in the context of a clinical trial or when other chemotherapeutic options have been exhausted.

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Gene-expression profiling of Waldenström macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma

Cited by 162 publications

References 39 publications

Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenström macroglobulinemia

Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique

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