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Karyotypic abnormalities and clinical aspects of patients with multiple myeloma and related paraproteinemic disorders
Abstract:
Karyotypic abnormalities were detected in the malignant cells of 6 of 18 patients with multiple myeloma (MM). Six patients with benign monoclonal gammopathy, one with amyloidosis of immunoglobulin origin, and two with Waldenström's macroglobulinemia had normal karyotypes. All six MM patients with aneuploidy were in a group of 10 patients in an accelerated or relapse phase of their disease and four had high serum paraprotein levels (7.92, 6.24, 6.80, and 4.24 g/dl, respectively) when their abnormal karyotypes were detected. Five of the 6 MM patients with aneuploidy had received prior chemotherapy. Aneuploidy was not observed in 8 stable MM patients. Abnormalities of chromosome 14 were present in all 6 patients, with a 14q+ marker in 5 and loss of No. 14 in 1. A translocation between Nos. 11 and 14 was found in aneuploid cells of 2 patients who had plasma cell leukemia (PCL). However, the break point in the long arm of No. 11 differed in the 2 patients. A gain of Nos. 5, 9, and 11 was seen in 3 patients, a gain of No 1 in 2, and rearrangements of No. 1 in 5 MM patients, including all 4 who had a 14q+ marker chromosome initially. A deletion of chromosome 6 at band q25 was detected in 2 MM patients and a pericentric inversion of No. 6 (6p21 to 6q13) was seen in the patient with PCL. Three of 4 MM patients had a nonrandom loss of one chromosome 8. Two other MM patients, who were treated with melphalan and prednisone, developed acute nonlymphocytic leukemia (ANLL) 2+ and 4+ years after the diagnosis of MM. Marrow cells of one patient showed a 5q- chromosome and a constitutional translocation involving Nos. 13 and 14 during the preleukemic stage; during the leukemic phase, the karyotype evolved to 50 chromosomes including extra chromosomes 1, 6, 8, 10, and 21 and a missing 7, in addition to the originally detected 5q- and the 13/14 translocation. The peripheral blood from the other patient was hypodiploid, with a missing chromosome 7 and a translocation between 3q and 9p. These patterns of chromosome change resemble those of ANLL rather than MM and are similar to the changes seen in ANLL after treated malignant lymphoma.
Insights
Karyotypic abnormalities, particularly involving chromosome 14, are linked to aggressive multiple myeloma (MM) phases. These chromosomal changes, including aneuploidy, were absent in stable MM and related disorders.
Area of Science:
- Hematology
- Cytogenetics
- Oncology
Background:
- Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of plasma cells.
- Understanding the cytogenetic landscape of MM is crucial for prognostication and therapeutic strategies.
Observation:
- Karyotypic abnormalities were identified in 6 of 18 multiple myeloma patients.
- Aneuploidy was exclusively observed in patients with accelerated or relapsed MM, often with high paraprotein levels and prior chemotherapy exposure.
- Normal karyotypes were found in benign monoclonal gammopathy, amyloidosis, and Waldenström's macroglobulinemia.
Findings:
- Chromosome 14 abnormalities, including 14q+ markers and loss of chromosome 14, were present in all 6 MM patients with aneuploidy.
- Translocations involving chromosomes 11 and 14 were noted in plasma cell leukemia (PCL) patients.
- Specific chromosomal gains (e.g., 1, 5, 9, 11) and losses (e.g., chromosome 6q25 deletion, chromosome 8 loss) were observed in subsets of MM patients.
- Two MM patients developed acute nonlymphocytic leukemia (ANLL), exhibiting chromosomal changes characteristic of ANLL rather than MM.
Implications:
- Cytogenetic analysis can aid in distinguishing aggressive MM from indolent forms and related plasma cell disorders.
- The observed chromosomal abnormalities may serve as potential biomarkers for disease progression and therapeutic response in multiple myeloma.
- The development of ANLL in MM patients treated with chemotherapy highlights the importance of monitoring for secondary malignancies and their distinct cytogenetic profiles.