Genomic Comparison Of Clonal B-Cells In Waldenstrom Macroglobulinemia (WM) Versus IgM MGUS

It is hypothesized that similarly to multiple myeloma, also in WM there may be a continuum between IgM MGUS, smoldering (SWM) and symptomatic WM, rather than these entities being considered as separate. The very low frequency of MYD88 L265P initially reported in IgM MGUS suggested that this could be...

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Published in:Blood 2013-11, Vol.122 (21), p.400-400
Main Authors: Paiva, Bruno, Corchete, Luis A, Gutierrez, Norma, Vidriales, María-Belén, Aires-Mejia, Irene, Sanchez, Maria Luz, Barcena, Paloma, Jimenez, Cristina, Garcia-Sanz, Ramon, Ocio, Enrique M., Escalante, Fernando, Hernandez, Jose, Cuello, Rebeca, Garcia de Coca, Alfonso, Sierra, Magdalena, Montes, Maria-Carmen, Gonzalez-Lopez, Tomas Jose, Galende, Josefina, Bárez, Abelardo, Alonso, Jose M, Pardal, Emilia, Orfao, Alberto, Mateos, Maria-Victoria, San Miguel, Jesus F
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Language:English
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Summary:It is hypothesized that similarly to multiple myeloma, also in WM there may be a continuum between IgM MGUS, smoldering (SWM) and symptomatic WM, rather than these entities being considered as separate. The very low frequency of MYD88 L265P initially reported in IgM MGUS suggested that this could be implicated in disease transformation. However, using sensitive ASO-PCR a significant proportion of patients of patients with IgM MGUS already harbors the MYD88 mutation. Thus, the molecular mechanisms driving the malignant transformation of WM remain largely unknown. Here, we used high-sensitive 8-color multidimensional flow cytometry (MFC) to detect and sort the specific B-cell clone in BM samples (N=31) from a total of 22 newly-diagnosed WM patients (8 symptomatic, 14 SWM) as well as 9 patients with IgM MGUS. The later 9 cases had negative BM biopsy, but light-chain restricted clonal B-cells (typically CD22low, CD25+, sIgM+, LAIR1-) were identified by MFC (median 1.74%, range 0.2%-7.04%). MYD88 L265P was detected on FACS-sorted (purity ≥97%) clonal B-cells from 9/9, 13/14 and 7/8 IgM MGUS, SWM and WM patients, respectively. We first compared the genomic profile of clonal B-cells through high density Cytoscan750K array. Overall, IgM MGUS, SWM and WM patients showed a median of 2, 1.5, and 3 copy number abnormalities (CNA)/case, respectively [defined by >25 consecutive imbalanced markers/segment, >100Kb genomic size and
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V122.21.400.400