title: 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.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. therese.nilsson@klingen.lu.se <therese.nilsson@klingen.lu.se>
authors.forename: Therese
authors.initials: T
authors.lastname: Nilsson
authors.forename: Lars
authors.initials: L
authors.lastname: Nilsson
authors.forename: Stig
authors.initials: S
authors.lastname: Lenhoff
authors.forename: Lars
authors.initials: L
authors.lastname: Rylander
authors.forename: Ingbritt
authors.initials: I
authors.lastname: Astrand-Grundström
authors.forename: Bodil
authors.initials: B
authors.lastname: Strömbeck
authors.forename: Mattias
authors.initials: M
authors.lastname: Höglund
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.forename: Jan
authors.initials: J
authors.lastname: Westin
authors.forename: Felix
authors.initials: F
authors.lastname: Mitelman
authors.forename: Sten E W
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D002869:Chromosome Aberrations; D002890:Chromosomes, Human, Pair 20 / Q000648:ultrastructure; D003582:Cytogenetics; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D009101:Multiple Myeloma / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D010265:Paraproteinemias / Q000235:genetics; D011003:Ploidies; D013234:Stem Cells