Karyotype in multiple myeloma and plasma cell leukaemia

Weh, H. J.; Gutensohn, Kay; Selbach, Johannes; Kruse, Rolf; Wacker-Backhaus, G; Seeger, Doris R.; Fiedler, Walter; Fett, W; Hossfeld, Dieter K.

doi:10.1016/0959-8049(93)90071-m

Cited by 79 publications

(71 citation statements)

References 21 publications

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“…According to studies of acute myelocytic leukaemia, ALL and lung cancer, the deletion of the p18 gene is a rare phenomenon (Nakamaki et al, 1995;Okamoto et al, 1995;Takeuchi et al, 1995). Since multiple myeloma is characterized by enormous heterogeneity of cytogenetic abnormalities, structural abnormalities of chromosome 1 is frequently found at diagnosis and more aggressive state of the disease (Ankathil et al, 1995;Cigudosa et al, 1994;Lai et al, 1995;Weh et al, 1993). Recent cytogenetic studies of multiple myeloma revealed that the short arm of chromosome 1 was occasionally deleted, suggesting that a tumour suppressor gene on 1p is associated with the development and/or the progression of myeloma (Taniwaki et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

Analysis of the p16^INK4A, p15^INK4B and p18^INK4C genes in multiple myeloma

et al. 1997

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Summary.To study the structural integrity of the cyclindependent kinase inhibitors known as INK4A (p16), INK4B (p15) and INK4C (p18) in multiple myeloma, we examined 20 primary myeloma samples (including one case of plasma cell leukaemia) using polymerase chain reaction-single strand conformation polymorphism, and 17 samples were examined by Southern blot analysis. The plasma cell leukaemia sample had homozygous deletions of the p15 and p16 genes (6%). One myeloma case had a p15 gene homozygous deletion (6%) with an intact p16 gene. This sample also had a p18 homozygous deletion, suggesting that the deletion of both genes may be important in either the development or progression of myeloma. No point mutations of these INK4 genes were found in the 20 samples. This is the first report that indicates that deletions of p15, p16 and p18 genes occur in some individuals with multiple myeloma (2/17 cases).

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Section: Resultsmentioning

confidence: 99%

Analysis of the p16^INK4A, p15^INK4B and p18^INK4C genes in multiple myeloma

et al. 1997

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“…2,4,[17][18][19] A number of techniques have been investigated in order to increase the detection rate of abnormal clones; [2][3][4][5][6] nevertheless, a large number of normal karyotypes are still reported, mainly in smoldering diseases. 20 When only normal metaphases are identified, it has been shown that they originate from the normal hematopoietic component 2 and additional techniques, such as flow cytometry or interphase fluorescence in situ hybridization are able to detect genomic defects in almost all patients whatever the stage of disease. [20][21][22][23][24][25][26] We have analyzed the results obtained in a series of 81 MM patients with abnormal karyotypes.…”

Section: Discussionmentioning

confidence: 99%

“…These cytogenetic results are in agreement with previously reported large series regarding chromosome gains, and most structural abnormalities involving chromosomes 1, 11, 13 and 14. [2][3][4][17][18][19] . However, among breaks found in about 10% of patients, differences can be noted: implication of chromosome 19 reported as specific of MM 29 was found in only 9% of our patients.…”

Section: Discussionmentioning

confidence: 99%

“…1 Multiple myeloma (MM) is a B cell neoplasia characterized by the expansion of a malignant plasma cell population within bone marrow, often associated with a low mitotic index leading to difficulties in the cytogenetic detection of the malignant clone. [2][3][4][5][6] On a morphological and phenotypic basis, MM is considered as a unique but heterogeneous disease. [7][8][9] We report the cytogenetic results obtained in a series of 81 MM patients with abnormal karyotypes showing the presence of two different cytogenetic patterns and leading to the evidence that among MM patients with abnormal karyotypes, at least two groups with a different prognosis can be identified.…”

Section: Introductionmentioning

confidence: 99%

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Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases

Smadja¹,

Fruchart²,

Isnard

et al. 1998

Leukemia

144

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We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients with abnormal karyotypes. Most karyotypes were complex with numerical and structural abnormalities but the analysis of chromosomal abnormalities allowed identification of two cytogenetic patterns depending on the chromosome number: a first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and 19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near-tetraploid karyotypes. Structural abnormalities were present in all but five hyperdiploid karyotypes, and frequently involved lymphoid breakpoints: immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases). Numerous other structural aberrations were detected; the most frequent involved chromosome 1 and chromosome 13. Structural abnormalities were significantly more frequent in the second hypodiploid group. When analyzing the results obtained in the 60 patients studied at the time of diagnosis, a prognostic correlation was found between the cytogenetic pattern and overall survival: hyperdiploid patients had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid group (median survival 36.8 vs 18.2 months, P Ͻ 0.04). These results suggest that MM could correspond to two closely related diseases.

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“…Chromosome changes in multiple myeloma are far from well characterized, mainly due to the low mitotic index which results in a small number of metaphases suitable for analysis. Still, more than 1000 cases of MM and related disorders with detailed cytogenetics have been reported (Dewald et al, 1985;Weh et al, 1993;Cigudosa et al, 1994;Taniwaki et al, 1994;Smadja et al, 1995;Laï et al, 1995;Sawyer et al, 1995;Calasanz et al, 1997) and some chromosome features can be summarized. (a) The proportion of abnormal karyotypes is about 40%, but varies between 20% and 60% depending on the series.…”

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confidence: 99%

Hypodiploidy and 22q11 rearrangements at diagnosis are associated with poor prognosis in patients with multiple myeloma

et al. 1997

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Summary.Our aim was to evaluate the clinical use of cytogenetic analysis as a prognostic factor in the outcome of newly diagnosed multiple myeloma (MM) patients. The present series includes 111 newly diagnosed MM patients treated with one of three standard-dose regimens or autologous transplantation over an 8-year time interval. As expected, the presence of an abnormal karyotype (39% of patients) correlated with poor prognosis (progression rate 63% v 47%, P ¼ 0 . 042), shorter event-free (EFS, P ¼ 0 . 014) and overall (OS, P ¼ 0 . 005) survival. Two distinct cytogenetic abnormalities were the most significant variables that influenced EFS and OS in the univariate analysis. The presence of hypodiploid karyotypes or rearrangements of band 22q11 were associated with higher progression rate (P ¼ 0 . 001) and shorter EFS (P < 0 . 024) and OS (P < 0 . 004). The median EFS and OS for patients with hypodiploidy was 4 and 7 months respectively. Multivariate analysis showed that absence of hypodiploidy was the most favourable prognostic variable for OS (P ¼ 0 . 022) followed by stage рIIA, serum calcium р2875 mmol/l, and absence of abnormalities 22q. The data suggest that the presence of hypodiploid karyotypes and rearrangements on 22q11 band show a higher progression rate and shorter survival in MM patients.

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Karyotype in multiple myeloma and plasma cell leukaemia

Cited by 79 publications

References 21 publications

Analysis of the p16^INK4A, p15^INK4B and p18^INK4C genes in multiple myeloma

Analysis of the p16^INK4A, p15^INK4B and p18^INK4C genes in multiple myeloma

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases

Hypodiploidy and 22q11 rearrangements at diagnosis are associated with poor prognosis in patients with multiple myeloma

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Karyotype in multiple myeloma and plasma cell leukaemia

Cited by 79 publications

References 21 publications

Analysis of the p16INK4A, p15INK4B and p18INK4C genes in multiple myeloma

Analysis of the p16INK4A, p15INK4B and p18INK4C genes in multiple myeloma

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases

Hypodiploidy and 22q11 rearrangements at diagnosis are associated with poor prognosis in patients with multiple myeloma

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Analysis of the p16^INK4A, p15^INK4B and p18^INK4C genes in multiple myeloma

Analysis of the p16^INK4A, p15^INK4B and p18^INK4C genes in multiple myeloma