MDS/AML‐associated cytogenetic abnormalities in multiple myeloma and monoclonal gammopathy of undetermined significance: Evidence for frequent de novo occurrence and multipotent stem cell involvement of del(20q)

Abstract

Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are characterized cytogenetically by 14q32 rearrangements, -13/13q-, and various trisomies. Occasionally, karyotypic patterns characteristic of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) occur in MM, often signifying therapy-related (t)-MDS/t-AML. Comparison of cytogenetic features in all published MMs (n = 993) and t-MDS/t-AML post-MM (n = 117) revealed significant differences in complexity and ploidy levels and in most genomic changes. Thus, these features often can be used to distinguish between MM and t-MDS/t-AML. Rarely, myeloid-associated aberrations are detected in MM without any signs of MDS/AML. To characterize such abnormalities in MM/MGUS, we ascertained all 122 MM and 26 MGUS/smoldering MM (SMM) cases analyzed in our department. Sixty-six (54%) MMs and 8 (31%) MGUS/SMMs were karyotypically abnormal, of which 6 (9%) MMs and 3 (38%) MGUS/SMMs displayed myeloid abnormalities, that is, +8 (1 case) and 20q- (8 cases) as the sole anomalies, without any evidence of MDS/AML. One patient developed AML, whereas no MDS/AML occurred in the remaining 8 patients. In one MGUS with del(20q), fluorescence in situ hybridization analyses revealed its presence in CD34+CD38- (hematopoietic stem cells), CD34+CD38+ (progenitors), CD19+ (B cells), and CD15+ (myeloid cells). The present data indicate that 20q- occurs in 10% of karyotypically abnormal MM/MGUS cases and that it might arise at a multipotent progenitor/stem cell level.

Frequent upregulation of MYC in plasma cell leukemia

“…Cytogenetic analysis and aCGH showed that the karyotype and the genomic profile of the majority of these cases was complex. Other studies had reported that cytogenetic changes were more frequent in PCL than in MM (Gutierrez et al, 2001;Smadja et al, 2003;Nilsson et al, 2004). Our data confirms that some PCL cases are extremely complex, although some show relatively simple changes.…”

Mosaic chromosome 20q deletions are more frequent in the aging population

“…Previous studies have detected del(20q) in stem cells with both myeloid and lymphoid differentiation capabilities. 24,25 Several non-neoplastic conditions have also been associated with del(20q), including idiopathic thrombocytopenic purpura, 26 pure red blood cell aplasia, 27 Schwachman-Diamond syndrome, 24 and idiopathic cytopenia. 28 In prior studies of cases of myeloid neoplasms, the presence of del(20q) alone or accompanied with one other chromosomal abnormality has been associated with favorable prognosis.…”

Simultaneous and Sequential Concurrent Myeloproliferative and Lymphoproliferative Neoplasms

“…In plasmacytoma CD34 + /CD38 + progenitor cells and granulocytic cells can be of the same clonal origin [57]. A common clonal origin has been demonstrated in post-plasmacytoma MDS [72], which is a remarkable setting because, in this context, a secondary therapy-associated MDS is usually considered [25,33,52,66].…”

“…It has been previously suspected [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91], but not systematically evaluated and proven, that Ph – MPN-B-CLL is the most common combination in patients with two different haematological neoplasms (fig. 3; online suppl.…”