Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate the diagnostic importance of the megakaryocytic morphology in the 5q- syndrome we studied the bone marrow from 48 unselected patients with myelodysplastic syndromes (MDS). 44 cases were primary and 4 secondary to cytostatic drug treatment or irradiation. There were 24 cases with chromosome anomalies, of whom 10 had del (5q). 4 of these had refractory anaemia (RA) with 5q- as the sole anomaly (group A), 2 had RA with 5q- and additional chromosome anomalies consisting of trisomy 8 (group B); 3 patients had RA with excess of blasts (RAEB) and complex, karyotypic changes also including 5q- (group B). Changes of the same type were found in 1 case of multiple myeloma with secondary MDS. All 6 RA patients with 5q- had characteristic megakaryocytes. More than 50% of the cells had no more than 2 nuclear segments, and predominantly had a diameter of 30 micron or more. No other patient with RA showed this picture. Only 1 patient with RAEB 5q- in group B had the same megakaryocytic changes. We conclude that diagnosis of a 5q- syndrome may be strongly suspected in cases of RA with these bone marrow changes. In cases of RAEB 5q- group B the bone marrow examination did not reveal the same consistent changes.
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PMID:Application of megakaryocytic morphology in diagnosing 5q- syndrome. 320 66

A case of acute nonlymphocytic leukemia (ANLL) occurring 2 years after the diagnosis of multiple myeloma (MM) that had been treated by only one course of melphalan/prednisone chemotherapy is reported. Cytogenetic and fluorescence in situ hybridization analysis of peripheral blood cells revealed trisomy 8 as the sole cytogenetic defect at the time of diagnosis of ANLL. Two years earlier, when MM was diagnosed without any cytological evidence of co-existent myelodysplasia, chromosomal analysis of bone marrow cells showed the same pathological karyotype 47, XY, +8 in 14 of 20 mitoses studied. Our interpretation of this unusual cytogenetic finding is that at the time of diagnosis of MM, in spite of lacking cytological signs of myelodysplasia, an unrecognizable myelodysplastic syndrome must have been present which then evolved to ANLL.
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PMID:Trisomy 8 preceding diagnosis of acute nonlymphocytic leukemia by 2 years in a patient with multiple myeloma without cytological evidence of myelodysplasia. 859 11

Plasma cell leukemia (PCL) is a very rare variant of multiple myeloma (MM) occurring in about 2% of newly diagnosed patients. Plasma cell leukemia may develop during the course of MM (secondary PCL) or it can occur without any prior sign of MM (primary PCL). We report a case of aggressive primary PCL with unusual clinical, cytogenetic and molecular features. A 36-year-old male patient was first seen because of fever and bone pain. On the skin of his chest, back, abdomen, and palpebras, there were nodular infiltrations resembling urticaria. White blood cell count was 10.8 x 10(9)/l with 41% plasmacytes. Bone marrow aspiration was hypercellular, 93.5% of cells were atypical plasmacytes and plasmablasts. The cytogenetic analysis of G-banded chromosomes in bone marrow cells yielded the trisomy 8. The skin biopsy specimen showed intensive infiltrates of uninucleated blastic cells similar to those found in the bone marrow. Immunophenotyping of bone marrow and skin neoplastic cells showed CD45+, CD45Ro+, CD68+, CD38+ and cytoplasmic kappa light chain +. The neoplastic cells stained negatively for lambda light chain, CD3, CD20, CD30, EMA, CD15, CD34, CD56 and factor VIII. The pattern of IgL genes rearrangement in the bone marrow aspirate, peripheral blood mononuclear cells, and skin specimens was examined by PCR analysis. All studied specimens showed three different IgK gene configurations suggesting that the neoplastic cells originated as a result of oligoclonal lymphoproliferation process. The patient received two courses of VAD (vincristine, doxorubicin, dexamethasone) without improvement and three courses of CHOP with only temporary stabilization of the disease. He died 5 months after the diagnosis of PCL because of disease progression and pneumonia.
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PMID:Aggressive primary plasma cell leukemia with skin manifestations, trisomy 8 and molecular oligoclonal features. 1214 88

Cytogenetic abnormalities (CA), especially of chromosome 13, have been used to identify a subgroup of previously untreated multiple myeloma (MM) patients with very poor prognosis despite high-dose therapy (HDT). We examined the prognostic implications of CA in 1000 MM patients receiving melphalan-based tandem autotransplants (median follow-up, 5 years). Negative consequences for both overall survival (OS) and event-free survival (EFS) in the presence of any CA were confirmed, especially when detected within 3 months of HDT. In the context of standard prognostic factors (SPF), 'MM-MDS' (MM karyotype that contains, in addition, CA typical of MDS) imparted a poor OS and EFS, after adjusting for any CA and all individual CA. One-year mortality was also high, especially for the MM-MDS subgroup with trisomy 8 within a MM signature karyotype (87%vs 34% in its absence, P < 0.001). No patient remained event free 5 years post transplant in the presence of these baseline high-risk CA. However, certain trisomies (e.g. chromosomes 7 and 9) and del 20 had favourable clinical consequences. The higher risk that is associated with CA compared with SPF justifies routine cytogenetic studies in all patients with MM at diagnosis and whenever additional treatment decisions are considered, such as in planning HDT either for initial response consolidation, at the time of primary unresponsiveness to induction therapy, or at relapse.
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PMID:MDS-type abnormalities within myeloma signature karyotype (MM-MDS): only 13% 1-year survival despite tandem transplants. 1287 70

Chromosome 1 pericentromeric heterochromatin (1q) has been shown to play an important role in the pathogenesis of non-Hodgkin lymphoma and multiple myeloma. Myelodysplastic syndrome (MDS) results from marrow failure in two or more cell lineages. Although trisomy 1q has been reported in MDS, it is usually present with additional common abnormalities such as trisomy 8, monosomy 5 or monosomy 7, leading to speculation that 1q abnormalities are mostly secondary events representing clonal evolution. We report two cases of MDS in which consistent involvement of 1q heterochromatin is seen as the primary clonal abnormality. Both patients presented with fatigue and pancytopenia. Based on the published reports and our cases, we propose that the 1q heterochromatin plays a vital role in the pathophysiology of MDS. Abnormalities involving 1q result in aberrant heterochromatin/euchromatin junctions, leading to gene dosage abnormalities. Further studies of 1q abnormalities in MDS might provide specific insights as to the exact role of the excess 1q heterochromatin in the etiology of MDS.
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PMID:Role of chromosome 1 pericentric heterochromatin (1q) in pathogenesis of myelodysplastic syndromes: report of 2 new cases. 1833 74

A 96-year-old woman with a 5-year history of multiple myeloma was admitted to our hospital because of increasing fatigue and fever. Bone marrow plasma cell analysis showed t(11;14), del(13q), and del(17p13). Her condition deteriorated, and she developed plasmacytosis resembling plasma cell leukemia. Chromosome analysis showed trisomy of chromosome 8 in the circulating plasma cells. The plasmacytosis resolved spontaneously without chemotherapy after about 5 weeks, and the trisomy became undetectable. The findings suggest that trisomy 8 might have contributed to the transient plasmacytosis, and that chromosome 8 carries genes associated with plasma cell proliferation, maturation, and apoptosis.
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PMID:Transient Plasmacytosis With Trisomy of Chromosome 8 in a Patient With Multiple Myeloma: A Case Report. 2914 55

Clinically and genomically, plasma cell myeloma (PCM) is a complex disease affecting the elderly population and has often had a poor prognosis. Karyotypic analysis of tumor cells is somewhat limited due to a low proliferative index coupled with a low frequency of tumor cells in clinical samples. Nevertheless, complex karyotypes with a multitude of numerical, balanced and unbalanced structural aberrations have been reported in these tumors. In this study we evaluated the karyotypes obtained in a single institution to identify recurring cytogenetic abnormalities. We constructed evolutionary pathways to differentiate abnormalities present at the beginning of evolution from those that developed later in evolution. We then estimated genetic progression scores and the clinical impact of the cytogenetic abnormalities on survival. In addition, we also evaluated the clinical significance of MYC related abnormalities (translocations and numerical changes) in disease evolution and on survival. Our results indicate that PCM with MYC related abnormalities in general have advanced tumors and adverse outcomes even with low proliferation. Trisomy 8 also contributes to unfavorable outcomes in PCM, this has not been reported previously.
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PMID:Clinical impact of MYC abnormalities in plasma cell myeloma. 3055 64