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)

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. © 2004 Wiley‐Liss, Inc.