Frequent Clonal Evolution in Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3919-3919
Author(s):  
Sang Mee Hwang ◽  
Jungeun Choi ◽  
Sunhee Yim ◽  
Tae Young Kim ◽  
Chaja See ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factors ◽  
In Situ Hybridization ◽  
Clonal Evolution ◽  
Chromosome 1 ◽  
Structural Abnormalities ◽  
Conventional Cytogenetics

Abstract Abstract 3919 Background: Multiple myeloma is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated B cells. Various complex cytogenetic and molecular genetic aberrations are present that are important for prognostication and follow up investigation. We investigated the clonal evolution of multiple myeloma patients at relapse or at progression compared from the diagnosis by conventional cytogenetics, fluorescence in situ hybridization (FISH) and cytoplasmic immunoglobulin fluroscence in situ hybridization (cIg FISH). Methods: 35 patients diagnosed as multiple myeloma by bone marrow examination from January 2003 to March 2011 were included. Conventional cytogenetics were performed in all patients at diagnosis and at relapse or progression. FISH was performed in 24 patients with available specimen for at least 3 items including −13/del(13q), p53 deletion/del(17p), 1q21 gain, p16 deletion, IgH rearrangement, t(4;14) and t(14;16). The FISH results were confirmed with cytoplasmic immunoglobulin FISH specifically staining plasma cells. Results: Forty-nine percent of the patients had relapsed or progressed with additional clonal evolutions and they were detected by conventional cytogenetics. Numerical abnormalities were more frequent than structural abnormalities and structural abnormalities involving chromosome 1 was frequent. Thirty-five percent had developed −13/13q loss which is considered a poor prognostic factor. cIg-FISH found additional aberrations in 20% of the patients such as RB1 deletion, del(17p) and t(14;16). Conclusion: Conventional cytogenetics and cIG-FISH are both necessary in relapsed patient since clonal evolutions develop in many patients which may only be detected by one method. Full evaluation of cIg-FISH including non-poor prognostic factors may be considered since new clones evolve that can be a candidate of follow-up marker and since prognostic factors can change as treatment modality changes. Disclosures: No relevant conflicts of interest to declare.

Pre-Transplantation Level of Minimal Residual Disease Detected by Quantitative Real-Time IgH-PCR Is a Prognostic Parameter in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4871-4871
Author(s):  
Roland Fenk ◽  
Mark Korthals ◽  
Guido Kobbe ◽  
Ulrich Steidl ◽  
Thorsten Graef ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factors ◽  
Tumor Cells ◽  
Residual Disease ◽  
Residual Tumor ◽  
Prognostic Group ◽  
Tumor Level ◽  
Minimal Residual

Abstract Background: High-dose chemotherapy with autologous stem cell transplantation has improved outcome and survival of patients with multiple myeloma. However, the majority of patients suffer from relapse. Using real-time quantitative (RQ) PCR we have shown before (Haematologica 89,2004) that the amount of residual tumor cells in the bone marrow of patients before transplantation is of prognostic relevance. In this study we evaluated in a larger group of patients with multiple myeloma whether a pre-transplantation level of clonotypic cells in the bone marrow is predictive for time-to-progression (TTP) and overall survival (OS). Further, we compared results with known prognostic factors. Patients and Methods: Bone marrow samples of 19 patients with stage II/III multiple myeloma were obtained after induction therapy but before transplantation. Immunoglobulin heavy chain (IgH) RQ-PCR using patient-specific Taqman probes was performed to quantify pre-transplantation tumor levels. The proportion of clonotypic cells was assessed as IgH/2 beta-actin ratio in percent. Medical records of patients were reviewed for prognostic factors and outcome. Results: The median level of residual tumor cells in bone marrow of all patients at the time before transplantation was 0.3 %. At 23 month median follow-up after transplantation the median TTP and OS in our study were 14 and 36 month, respectively. The threshold level of 0.03% clonotypic cells identified two prognostic groups (p<0.0001, log rank). Twelve patients in the bad prognostic group had an early relapse with a median TTP of 9 month (range: 3 – 17 month). All patients in the good prognostic group (n=7) had ongoing remissions after a median follow-up of 24 month (range: 13–44 month). Univariat analysis was performed including other prognostic factors at the time before transplantation such as cytogenetic abnormalities, beta2-microglobulin, hemoglobulin, platelet count, LDH, CRP, serum albumine and age. Besides the pre-transplant level of minimal residual disease, CRP level was predictive for TTP. In multivariat analysis using a step-wise cox regression model grouping by pre-transplantation tumor level was the only prognostic factor for TTP (p = 0.05). Moreover, low pre-transplantation tumor levels also showed a trend for a better OS, but in multivariat analysis only normal cytogenetics were predictive for a superior outcome (p = 0.03). Conclusion: Quantitative molecular assessment of pre-transplantation tumor level in the bone marrow is an independent prognostic parameter for the progression-free survival of patients with multiple myeloma and thus helps to guide therapeutic interventions

Identification of New Nonrandom Translocations in Multiple Myeloma With Multicolor Spectral Karyotyping

Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 4269-4278 ◽  
Author(s):  
Jeffrey R. Sawyer ◽  
Janet L. Lukacs ◽  
Nikhil Munshi ◽  
K. Raman Desikan ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
In Situ Hybridization ◽  
Chromosome Aberrations ◽  
Chromosome Morphology ◽  
Spectral Karyotyping ◽  
Chromosome Translocations ◽  
Igh Locus ◽  
Additional Chromosome

Multicolor spectral karyotyping (SKY) was performed on bone marrow samples from 50 patients with multiple myeloma (MM) in anticipation of discovering new previously unidentified translocations. All samples showed complex karyotypes with chromosome aberrations which, in most cases, were not fully characterized by G-banding. Patients of special interest were those who showed add(14)(q32), add(8)(q24) and those whose G-banding karyotypes showed poor chromosome morphology. Three new recurring chromosome translocations not previously reported in MM were identified. Two of the translocations involve recurring aberrations at band 14q32.3, the site of the IgH locus, with different exchange partners. The most frequently recurring rearrangement was a subtle translocation at 14q32.3 designated as a t(14;16)(q32;q22∼23), which was identified in six patients. A second and larger translocation at 14q32, identified in two patients, was designated as a t(9;14)(p13;q32), previously associated with Waldenstrom’s macroglobulinemia and lymphoplasmacytoid lymphoma. A third translocation, identified in two patients, involved a whole-arm t(6;8)(p10;q10) translocation. The SKY technique was able to refine the designations of over 156 aberrations not fully characterized by G-banding in this study and resolved additional chromosome aberrations in every patient studied except two. The t(14;16)(q32;q22∼23) identified by SKY in this study suggests this may be a frequent translocation in MM associated with complex karyotypes and disease progression. Therefore, the SKY technique provides a useful adjunct to routine G-banding and fluorescence in situ hybridization studies in the cytogenetic analysis of MM.

scholarly journals Nonrandom chromosomal rearrangements of 14q32.3 and 19p13.3 and preferential deletion of 1p in 21 patients with multiple myeloma and plasma cell leukemia

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2283-2290 ◽  
Author(s):  
M Taniwaki ◽  
K Nishida ◽  
T Takashima ◽  
H Nakagawa ◽  
H Fujii ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Chromosomal Abnormalities ◽  
Chromosomal Rearrangements ◽  
Plasma Cell Leukemia ◽  
Chromosome 1 ◽  
Cell Leukemia ◽  
Structural Abnormalities ◽  
Break Points

Structural chromosomal abnormalities and their break-points were characterized in 17 patients with multiple myeloma (MM) and 4 with plasma cell leukemia by banding. Chromosome 14q32 translocations with a variety of partners were detected in 13 patients, and a variant translocation t(8;22)(q24.1;q11) was detected in 1. Three recurrent 14q32 translocations have been identified: t(6;14)(p21.1;q32.3) occurring in 3 cases, and t(11;14)(q13;q32.3) and t(14;18) (q32.3;q21.3) each occurring in 2 cases. Translocations t(1;14)(q21;q32.3), t(3;14)(p11;q32),t(7;14)(q11.2;q32.3), and t(11;14)(q23;q32.3) were found in each patient, whereas in the remaining 2 patients, partner chromosomes could not be determined. The band 19p13.3 was newly delineated as a recurrent breakpoint involved in translocations in MM. Chromosomes 1 and 6 were also commonly involved in structural abnormalities (14 and 10 patients, respectively), although no particular bands were noted. However, the short arm of chromosome 1 was preferentially involved in deletion, suggesting a certain antioncogene on 1p associated with the development of myeloma. In addition; fluorescence in situ hybridization was successfully applied to determine the nature of the structural abnormalities in a patient with t(8;22) translocation. The present findings suggest that there may be subsets of 14q32 translocations specific to MM.

Fluorescence In Situ Hybridization on Peripheral-Blood Specimens Is a Reliable Method to Evaluate Cytogenetic Response in Chronic Myeloid Leukemia

2000 ◽  
Vol 18 (7) ◽  
pp. 1533-1538 ◽  
Author(s):  
Steven Le Gouill ◽  
Pascaline Talmant ◽  
Noël Milpied ◽  
Axelle Daviet ◽  
Michèle Ancelot ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Cytogenetic Response ◽  
Response To Treatment ◽  
Interphase Fish ◽  
Conventional Cytogenetics ◽  
Blood Specimens

PURPOSE: To evaluate the usefulness of fluorescence in situ hybridization (FISH) on peripheral-blood specimens to evaluate the cytogenetic response to treatment in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: In a first attempt, we analyzed 62 bone marrow specimens using interphase FISH and compared the results with those of conventional cytogenetics. In a second step, we analyzed 60 paired sets of bone marrow and peripheral-blood specimens with interphase FISH. RESULTS: The results of interphase FISH agreed with conventional cytogenetics on bone marrow for most patients, and only minor differences were found (r = .98). The comparison of interphase FISH on bone marrow versus peripheral-blood specimens showed a strong correlation between these two specimen sources (r = .97). CONCLUSION: Our results confirmed that FISH is a sensitive technique for the evaluation of response to treatment in patients with CML. Moreover, our study suggests that follow-up of cytogenetic response to therapy can be evaluated on peripheral-blood specimens, thus enabling an easier and more frequent evaluation of patients. The next step will be to evaluate this technique in a large prospective trial to define the prognostic value of complete remissions evaluated by FISH.

The usefulness of interphase fluorescence in situ hybridization at diagnosis of myeloma in addition to metaphase cytogenetics

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19558-e19558
Author(s):  
S. Park ◽  
C. Kim ◽  
H. Kim ◽  
D. Hong ◽  
S. Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Plasma Cells ◽  
Chromosomal Abnormalities ◽  
Chromosome Abnormalities ◽  
Interphase Fish ◽  
Conventional Cytogenetics ◽  
Igh Rearrangement

e19558 Background: Multiple myeloma is characterized by the accumulation of malignant plasma cells within the bone marrow and regarded as incurable, but remissions may be induced with steroids, chemotherapy, thalidomide and stem cell transplants. The clinical heterogeneity of myeloma is dictated by the cytogenetic aberrations present in the clonal plasma cells. Fluorescence in situ hybridization (FISH) overcomes the limitations of standard cytogenetics and allows for the detection of numerical and structural chromosomal abnormalities in both metaphase spreads and interphase nuclei. Methods: We evaluated the chromosome abnormalities in 34 MM patients using conventional cytogenetics and interphase FISH with 6 probes such as IGH/CCND1, IGH/FGFR3, IGH/MAF, DS13S319/LAMP1, IGH/BAP, and p53/CEP17. Results: Cytogenetic abnormalities were found in 24 (70.6%) of the 28 MM patients. 10 (35.7%) patients had abnormal metaphases by conventional cytogenetics. Interphase FISH results were abnormal in 21 (61.8%) patients and 11 (52.3%) patients had abnormal interphase FISH but normal metaphases. The evidence of the loss of D13S319 with or without loss of LAMP1 was found in 6 (21.4%) patients, and loss of p53±CEP17 for 2 patients, IGH-BAP for 9 (26.5%) patients, IGH/FGFR3 for 2 patients, and IGH/CCND1 for 7 (20.6%) patients, respectively. However, there were none positive for IGH/MAF. Chromosome 13 abnormalities and IGH rearrangement is correlated with poor clinical outcome. Conclusions: Interphase FISH can provide useful information to evaluate the presence of prognostic chromosome abnormalities in addition to metaphase cytogenetics. And it should be used in the routine evaluation of multiple myeloma. No significant financial relationships to disclose.

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