Role of molecular-genetic abnormalities in pathogenesis and risk stratification of multiple myeloma
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Keywords

FISH
mSMART
multiple myeloma
cytogenetics

How to Cite

, , , , , , , , & . (2016). Role of molecular-genetic abnormalities in pathogenesis and risk stratification of multiple myeloma. Voprosy Onkologii, 62(4), 429–438. https://doi.org/10.37469/0507-3758-2016-62-4-429-438

Abstract

Over the past decades the studies have greatly improved our understanding of the molecular basis of multiple myeloma (MM) and mechanisms of disease progression. The majority of the most widespread chromosomal aberrations, revealing in MM, has independent predictive value and influence on a choice of optimal treatment. There were observed 190 MM patients in hematologic hospitals of St. Petersburg. Genetic anomalies (GA) were detected at 3l,3% of patients and did not depend on their age. Patients with ISS III had a detectability of GA higher than with ISS II and ISS I (48,°% (24/5°), 2l,2% (7/33) and 27,6% (8/29)). Translocation t(ll;l4) was found in 23,3% (3O/129) patients; dell3q - 20,8% (27/13°); dell7p - at 8,4% (7/83); t(4;l4) - at 6,9% (9/13O), that allowed to stratify patients in groups of risk according to mSMART version l. O and 2. O. Median overall survival (OS) modified mSMART l. O in group of standard risk was 7° months, high risk - 47,l months. Median OS mSMART 2. O in group of standard risk was 7° months, intermediate risk - 47 months, high risk - 45 months. OS did not depend on age, clinical manifestations, treatment and other factors.
https://doi.org/10.37469/0507-3758-2016-62-4-429-438
PDF (Русский)

References

Абдулкадыров К. М. Гематология: Новейший справочник / Под общ. ред. К. М. Абдулкадырова. - СПб. : Изд-во Сова, 2004. - 928 с.

Руковицин О. А. Гематология: национальное руководство / Под ред. О. А. Рукавицына. - М. : ГЭОТАР-Медиа, 2015. - 776 с.

Avet-Loiseau H., Facon T., Daviet A. et al. 14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma // Cancer Res. - 1999. - Vol. 59, N 18. -P. 4546-4550.

Avet-Loiseau H., Li J. Y, Godon C. et al. P53 deletion is not a frequent event in multiple myeloma // Br J Haematol. -1999. - Vol. 106, N 3. - P. 717-719.

Avet-Loiseau H., Daviet A., Sauner S. et al. Chromosome 13 abnormalities in multiple myeloma are mostly monosomy 13 // Br J Haematol. - 2000. - Vol. 111, N 4. - P. 1116-1117.

Avet-Loiseau H. Role of genetic in prognostication in myeloma // Best Res Clin Haematol. - 2007. - Vol. 20, N 4. - P. 625-635.

Avet-Loiseau H., Attal M., Moreau P et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroup Francophone du Myeloma // Blood. - 2007. - Vol. 109, N 8. - P. 3489-3495.

Avet-Loiseau H., Soulier J., Fermand J. P et al. Impact of high-risk cytogenetics and prior therapy on out-comes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone // Leukemia. - 2010. - Vol. 24, N 3. - P. 623-628.

Balcarkova J., Urbankova H., Scudla V. et al. Gain of chromosome arm 1q in patients in relapse and progression of multiple myeloma // Cancer Genet Cytogenet. - 2009. -Vol. 192, N 2. - P. 68-72.

Bergsagel P. L., Kuehl W. M. Chromosome translocation in multiple myeloma // Oncogene. - 2001. - Vol. 20, N 40. - P. 5611-5622.

Bergsagel P. L., Kuehl W. M. Multiple myeloma: evolving genetic events and host interactions // Nature Reviews Cancer. - 2002. - Vol. 2, N 3. - P. 175-187.

Bergsagel P. L., Kuehl W. M. Molecular pathogenesis and a consequent classification of multiple myeloma // J Clin Oncol. - 2005. - Vol. 23, N 26. - P. 6333-6338.

Bergsagel P. L., Kuehl W. M., Zhan F. et al. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma // Blood. - 2005. - Vol. 106, N 1. -P. 296-303.

Boyd K. D., Ross F. M., Walker B. A. et al. Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32. 3 as being genes in regions associated with adverse survival // Clin Cancer Res. - 2011. - Vol. 17, N 24. - P. 7776-7784.

Chang H., Qi C., Yi Q. L. et al. P53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation // Blood. - 2005. -Vol. 105, N 1. - P. 358-360.

Chiecchio L., Protheroe R. K., Ibrahim A. H. et al. Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma // Leukemia. - 2006. - Vol. 20, N 9. - P. 1610-1617.

Dib A., Peterson T. R., Raducha-Grace L. et al. Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression // Cell Div. - 2006. - Vol. 1. - P. 23.

Drach J., Angerler J., Schuster J. et al. Interphase fluorescence in situ hybridization identifies chromosomal abnormalities in plasma cell from patients with monoclonal gammopathy of undetermined significance // Blood. -1995. - Vol. 86, N 10. - P. 3915-3921.

Elnenaei M. O., Gruzka-Westwood A. M., A’Hernt R., et al. Gene abnormalities in multiple myeloma; the relevance of TP53, MDM2, and CDKN2A // Haematologica. - 2003. -Vol. 88, N 5. - P. 529-537.

Fonseca R., Ahmann G. J., Juneau A. L. et al. Cytogenetic abnormalities in multiple myeloma and related plasma cell disorders: a comparison of conventional cytogenetics to fluorescent in situ hybridization with simultaneous cytoplasmic immunoglobulin staining // Blood. - 1997. - Vol. 90, N1. - P. 349a.

Fonseca R., Coignet L. J., Dewald G. W. Cytogenetic abnormalities in multiple myeloma // Hematol Oncol Clin North Am. - 1999. - Vol. 13, N 6. - P. 1169-1180.

Fonseca R., Debes-Marun C. S., Picken E. B. et al. The recurrent IgH translocation are highly associated with nonhyperdiploid variant multiple myeloma // Blood. -2003. - Vol. 102, N 7. - P. 2562-2567.

Fonseca R., Barlogie B., Bataille R. et al. Genetics and cytogenetics of multiple myeloma: a workshop report // Cancer Res. - 2004. - Vol. 64, N 4. - P. 1546-1558. 11

Fonseca R., Bersagel P. L., Drach J. et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review // Leukemia. - 2009. -Vol. 23, N 12. - P. 2210-2221.

Garifullin A. D., Martynkevich I. S, Voloshin S. V. et al. The impact of genetic abnormalities on survival in patients with newly diagnosed multiple myeloma // The 1st World Congress on Controversies in Multiple Myeloma Abstract book. - 2014. - 27 p.

Gertz M. A., Lacy M. Q., Dispenzieri A. et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16. 3;q32), and -17p13 in myeloma patients treated with high-dose therapy // Blood. - 2005. - Vol. 106, N 8. - P. 2837-2840.

Gonzalez-Paz N., Chng W. J., McClure R. F. et al. Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications // Blood. - 2007. - Vol. 109, N 3. - P. 1228-1232.

Kumar S. K., Rajkumar S. V., Dispenzieri A. et al. Improved survival in multiple myeloma and the impact of novel therapies // Blood. - 2008. - Vol. 111, N 5. - P. 2516-2520.

Kumar S. K., Mikhael J. R., Buadi F. K. et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines // Mayo Clin Proc. - 2009. - Vol. 4, N 12. - P. 1095-1110.

Kumar S., Fonseca R., Ketterling P. R. et al. Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics // Blood. - 2012. - Vol. ; 119, N 9. - P. 2100-2105.

Lode L., Eveillard M., Trichet V. et al. Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma // Haematologica. - 2010. - Vol. 95, N 11. - P. 1973-1976.

Mikhael J. R., Dingli D., Roy V. et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013 // Mayo Clin Proc. - 2013. - Vol. 88, N 7. - P. 360-376.

Moreau P., Attal F., Garban F., et al. Heterogeneity of t(4;14) in multiple myeloma. Long-term-up of 100 cases treated with tandem transplantation in IFM99 trials // Leukemia. - 2007. - Vol. 21, N 9. - P. 2020-2024.

Nemec P., Zemanova Z., Greslicova H. et al. Gain of 1q21 is an unfavorable genetic prognosis factor for multiple myeloma patients treated with high-dose chemotherapy // Biol Blood Marrow Transplant. - 2010. - Vol. 16, N 4. - P. 548-554.

Pichorri F., Suh S.-S., Rocci A. et al. Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development // Cancer Cell. - 2010. - Vol. 18, N 4. -P. 367-381.

Qazilbash M. H., Saliba R. M., Ahmed B. et al. Deletion of the short arm of chromosome 1 (del 1p) as a strong predictor of poor outcome in myeloma patients undergoing an autotransplant // Biol Marrow Transplant. - 2007. - Vol. 13, N 9. - P. 1066-1072.

Seong C., Delasalle K., Hayes K. et al. Prognostic value of cytogenetics in multiple myeloma // Br J Haematol. - 1998. - Vol. 101, N 1. - P. 189-194.

Smadja N. V., Fruchart C., Isnard F. et al. Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different disease // Leukemia. - 1998. - Vol. 12, N 6. -P. 960-969.

Tiedemann R. E., Gonzalez-Paz N., Kyle R. A. et al. Genetic aberrations and survival in plasma cell leukemia // Leukemia. - 2008. - Vol. 22, N 5. - P 1044-1052.

Tricot G., Sawyer J. R., Jagannath S. et al. Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants // J Clin Oncol. - 1997. - Vol. 15, N 7. - P. 2659-2666.

Walker B. A., Leone P E., Chiecchio L. et al. A compendium of myeloma associated chromosomal copy number abnormalities and their prognostic value // Blood. - 2010. - Vol. 116, N 15. - P 56-65.

Zhou Y, Nair B., Shaughnessy Jr. J. et al. Cytogenetic abnormalities in multiple myeloma: poor prognosis linked to concomitant detection in random and focal lesion bone marrow samples and associated with high-risk gene expression profile // Br J Haematol. - 2009. - Vol. 145, N 5. - P 637-641.

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