Prognostic value of 1q21 amplification in multiple myeloma


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Abstract

Aim. To determine the prevalence of amp1q21 and its relationship to the clinical manifestations of multiple myeloma (MM). Subjects and methods. In December 2009 to March 2016, a total 134 patients aged 30 to 81 years (median 57 years) underwent a pretreatment FISH-study of bone marrow (BM) with centromeric and locus-specific DNA probes to identify amp1q21, t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), trisomies of chromosomes 5, 9, 15, del13q14, del17p13/TP53, and t(8q24)/cMYC. Induction therapy with bortezomib-containing cycles was performed. Autologous stem cell transplantation was carried out in 48 patients. The median follow-up of patients was 19.3 months (3.2—77.4 months). Disease progression was diagnosed in 69 (51.5%) patients; 12 patients also underwent FISH study during disease progression. Results. At the onset of MM, amp1q21 was detected in 53 (39.6%) patients. The overall 5-year survival rate in patients with amp1q21 was almost 2 times lower than that in those without amp1q21 (43.5 and 79.4%, respectively; p=0.07). The overall 5-year survival rate in patients with one extra copy of 1q21 (only 3 copies) was 67.3%, that in those with 2 or more extra copies of 1q21 (only 4—7 copies) was 20.9% (p=0.0016). Nine (75%) of the 12 patients examined during disease progression were found to have amp1q21: 2 cases were detected in the period of progression to have amp1q21 in its absence at disease onset; 7 cases had amp1q21 both at MM onset and progression; however, the number of copies of 1q21 was unchanged. Conclusion. Аmp1q21 is one of the most common chromosomal abnormalities in patients with new-onset MM and may appear in the course of disease progression. The presence of аmp1q21 is an important prognostic factor and must have to be included in the diagnostic study both at disease onset and progression.

About the authors

T V Abramova

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

T N Obukhova

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

L P Mendeleeva

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

O S Pokrovskaya

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

E O Gribanova

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

V V Ryzhko

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

L A Grebenyuk

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

M V Nareyko

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

M V Solovyev

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

O M Votyakova

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России

Москва, Россия

S M Kulikov

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

M A Rusinov

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

V G Savchenko

ФГБУ «Гематологический научный центр» Минздрава России

Москва, Россия

References

  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
  2. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011; 117(19):5019-5032. https://doi.org/10.1182/blood-2011-01-293050
  3. Nemec P, Zemanova Z, Greslikova H, Greslikova H, Michalova K, Filkova H, Tajtlova J, Kralova D, Kupska R, Smetana J, Krejci M, Pour L, Zahradova L, Sandecka V, Adam Z, Buchler T, Spicka I, Gregora E, Kuglik P, Hajek R. Gain of 1q21 Is an Unfavorable Genetic Prognostic Factor for Multiple Myeloma Patients Treated with High-Dose Chemotherapy. Biol Blood Marrow Transplant. 2010;16(4):548-554. https://doi.org/10.1016/j.bbmt.2009.11.025
  4. Kuehl WM, Bergsagel PF. Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest. 2012;122(10):3456-3463. https://doi.org/10.1172/jci61188
  5. Mahindra A, Laubach J, Raje N, Munshi N, Richardson PG, Anderson K. Latest advanced and current challenges in the treatment of multiple myeloma. Nat Rev Clin Oncol. 2012;9(3):135-143. https://doi.org/10.1038/nrclinonc.2012.15
  6. Hervé AL, Florence M, Philippe M, Michel A, Thierry F, Kenneth A, Jean-Luc H, Nikhil M, Stéphane M. Molecular heterogeneity of multiple myeloma: pathogenesis, prognosis, and therapeutic implications. J Clin Oncol. 2011;29(14):1893-1897. https://doi.org/10.1200/jco.2010.32.8435
  7. Fonseca R, Debes-Marun CS, Picken EB, Dewald GW, Bryant SC, Winkler JM, Blood E, Oken MM, Santana-Dávila R, González-Paz N, Kyle RA, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood. 2003;102(7):2562-2567. https://doi.org/10.1182/blood-2003-02-0493
  8. Morgan GJ, Walker BA and Davies FE. The genetic architecture of multiple myeloma. Nature Reviews Cancer. 2012;12(5):335-348. https://doi.org/10.1038/nrc3257
  9. Avet-Loiseau H, Leleu X, Roussel M, Moreau P, Guerin-Charbonnel C, Caillot D, Marit G, Benboubker L, Voillat L, Mathiot C, Kolb B, Macro M, Campion L, Wetterwald M, Stoppa AM, Hulin C, Facon T, Attal M, Minvielle S, Harousseau JL. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010;28(30):4630-4634. https://doi.org/10.1200/jco.2010.28.3945
  10. Bergsagel PL, Kuehl WM. Chromosome translocations in multiple myeloma. Oncogene. 2001;20(40):5611-5622. https://doi.org/10.1038/sj.onc.1204641
  11. DeWald GW, Kyle RA, Hicks GA, Greipp PR. The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis. Blood. 1985;66(2):380-390.
  12. Kumar S, Fonseca R, Ketterling RP, Dispenzieri A, Lacy MQ, Gertz MA, Hayman SR, Buadi FK, Dingli D, Knudson RA, Greenberg A, Russell SJ, Zeldenrust SR, Lust JA, Kyle RA, Bergsagel L, Rajkumar SV. Trisomies in multiple myeloma: Impact on survival in patients with high-risk cytogenetics. Blood. 2012;119(9):2100-2105. https://doi.org/10.1182/blood-2011-11-390658
  13. Nahi H, Sutlu T, Jansson M, Alici E, Gahrton G. Clinical impact of chromosomal aberrations in multiple myeloma. J Intern Med. 2010;269(2):137-147. https://doi.org/10.1111/j.1365-2796.2010.02324.x
  14. Ni IB, Ching NC, Meng CK, Zakaria Z. Translocation t(11;14) (q13;q32) and genomic imbalances in multi-ethnic multiple myeloma patients: a Malaysian study. Hematol Rep. 2012;4(3):e19. https://doi.org/10.4081/hr.2012.e19
  15. Segges P, Braggio E. Genetic Markers Used for Risk Stratification in Multiple Myeloma. Genet Res Int. 2011;2011:798089. https://doi.org/10.4061/2011/798089
  16. Ross FM, Chiecchio L, Dagrada G, Protheroe Rebecca K.M, Stockley DM, Harrison CJ, Cross Nicholas CP, Szubert AJ, Drayson MT, and Morgan GJ. The t(14;20) is a poor prognostic factor in myeloma but is associated with long term stable disease in MGUS. Haematologica. 2010;95(7):1221-1225. https://doi.org/10.3324/haematol.2009.016329
  17. Avet-Loiseau H, Attal M, Campion L, Caillot D, Hulin C, Marit G, Stoppa AM, Voillat L, Wetterwald M, Pegourie B, Voog E, Tiab M, Banos A, Jaubert J, Bouscary D, Macro M, Kolb B, Traulle C, Mathiot C, Magrangeas F, Minvielle S, Facon T, Moreau P. Longterm analysis of the IFM 99 trials for myeloma: Cytogenetic abnormalities [(t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin Oncol. 2012;30(16):1949-1952. https://doi.org/10.1200/jco.2011.36.5726
  18. Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR, Dispenzieri A, Fonseca R, Sher T, Kyle RA, Lin Y, Russell SJ, Kumar S, Bergsagel PL, Zeldenrust SR, Leung N, Drake MT, Kapoor P, Ansell SM, Witzig TE, Lust JA, Dalton RJ, Gertz MA, Stewart AK, Rajkumar SV, Chanan-Khan A, Lacy MQ. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013;88(4):360-376. https://doi.org/10.1016/j.mayocp.2013.01.019
  19. Avet-Louseau H, Daviet A, Sauner S, Bataille R. Intergroupe Francophone du Myélome. Chromosome 13 abnormalities in multiple myeloma are mostly monosomy 13. Br J Haematol. 2000;111(4):1116-1117. https://doi.org/10.1046/j.1365-2141.2000.02488.x
  20. Sawyer JR. The prognostic significance of cytogenetics and molecular profiling in multiple myeloma. Cancer Genet. 2011;204(1):3-12. https://doi.org/10.1016/j.cancergencyto.2010.11.002
  21. Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, Coy NN, Cook G, Russell NH, Rudin C, Roddie H, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012;119(1):7-15. https://doi.org/10.1182/blood-2011-06-357038
  22. An G, Xu Y, Shi L, Zhong S, Deng S, Xie Z, Sui W, Zhan F, and Qiu L. Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no prognostic value. Haematologica. 2013;99(2):353-359. https://doi.org/10.3324/haematol.2013.088211
  23. Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, Van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119(4):940-948. https://doi.org/10.1182/blood-2011-09-379164
  24. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548. https://doi.org/10.1016/s1470-2045(14)70442-5
  25. Miltenyi Biotec. Accessed March 1, 2016. Available at: http://www.miltenyibiotec.com
  26. Simons A, Shaffer LG, Hastings RJ. Cytogenetic Nomenclature: Changes in the ISCN 2013 Compared to the 2009 Edition. Cytogenet Genome Res. 2013;141:1-6. https://doi.org/10.1159/000353118
  27. Sawyer JR, Waldron JA, Jagannath S, Barlogie B. Cytogenetic findings in 200 patients with multiple myeloma. Cancer Genet Cytogenet. 1995;82(1):41-49. https://doi.org/10.1016/0165-4608(94)00284-i
  28. Stewart AK, Fonseca R. Prognostic and therapeutic significance of myeloma genetics and gene expression profiling. J Clin Oncol. 2005;23(26):6339-6344. https://doi.org/10.1200/jco.2005.05.023
  29. Zhan F, Colla S, Wu X, Chen B, Stewart JP, Kuehl WM, Barlogie B, Shaughnessy JD. CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Blood. 2007;109(11):4995-5001. https://doi.org/10.1182/blood-2006-07-038703
  30. Bahmanyar M, Qi X, Chang H. Genomic aberrations in anaplastic multiple myeloma: High frequency of 1q21(CKS1B) amplifications. Leuk Res. 2013;37(12):1726-1728. https://doi.org/10.1016/j.leukres.2013.09.025
  31. Zhang Y. CKS1B (CDC28 protein kinase regulatory subunit 1B). Atlas Genet Cytogenet Oncol Haematol. 2011;14(7):676-678. https://doi.org/10.4267/2042/44803
  32. Chang H, Jiang N, Jiang H, Saha MN, Qi C, Xu W, Reece D. CKS1B nuclear expression is inversely correlated with p27Kip1 expression and is predictive of an adverse survival in patients with multiple myeloma. Haematologica. 2010;95(9):1542-1547. https://doi.org/10.3324/haematol.2009.022210
  33. Denicourt C, Saenz CC, Datnow B, Cui Xian-Shu, Dowdy SF. Relocalized p27Kip1 Tumor Suppressor Functions as a Cytoplasmic Metastatic Oncogene in Melanoma. Cancer Res. 2007;67(19):9238-9243. https://doi.org/10.1158/0008-5472.can-07-1375
  34. Shaughnessy J. Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma. Hematology. 2005;10(Suppl.1):117-126. https://doi.org/10.1080/10245330512331390140
  35. Chen M-H, Qi C, Reece D, Chang H. Cyclin kinase subunit 1B nuclear expression predicts an adverse outcome for patients with relapsed/refractory multiple myeloma treated with bortezomib. Hum Pathol. 2012;43(6):858-864. https://doi.org/10.1016/j.humpath.2011.07.013
  36. Fonseca R, Van Wier SA, Chng WJ, Lacy MQ, Dispenzieri A, Bergsagel PL, Rajkumar SV, Greipp PR, Litzow MR, Price-Troska T, Henderson KJ, Ahmann GJ, Gertz MA. Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and increase CKS1B expression in myeloma. Leukemia. 2006; 20(11):2034-2040. https://doi.org/10.1038/sj.leu.2404403
  37. Yu W, Guo R, Qu X, Qiu H, Li J, Zhang R, Chen L. The amplification of 1q21 is an adverse prognostic factor in patients with multiple myeloma in a Chinese population. Onco Targets Ther. 2016;9:295-302. https://doi.org/10.2147/ott.s95381

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