ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients

被引：232

作者：

Patnaik, M. M. ^{[1
]}

Itzykson, R. ^{[2
,3
,4
]}

Lasho, T. L. ^{[1
]}

Kosmider, O. ^{[2
,5
]}

Finke, C. M. ^{[1
]}

Hanson, C. A. ^{[6
]}

Knudson, R. A. ^{[7
]}

Ketterling, R. P. ^{[7
]}

Tefferi, A. ^{[1
]}

Solary, E. ^{[3
,4
,8
]}

机构：

[1] Mayo Clin, Div Hematol, Rochester, MN 55905 USA

[2] Univ Paris 05, Paris, France

[3] Inst Gustave Roussy, Villejuif, France

[4] Univ Paris 11, Orsay, France

[5] Inst Cochin, Paris, France

[6] Mayo Clin, Div Hematopathol, Rochester, MN 55905 USA

[7] Mayo Clin, Cytogenet Div, Rochester, MN 55905 USA

[8] INSERM, U1009, Villejuif, France

来源：

LEUKEMIA | 2014年 / 28卷 / 11期

关键词：

ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; PRIMARY MYELOFIBROSIS; MYELOPROLIFERATIVE NEOPLASMS; SRSF2; MUTATIONS; GENE ASXL1; FREQUENT; KARYOTYPE; RELEVANCE; CBL;

D O I：

10.1038/leu.2014.125

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In a cohort of 466 patients, we sought to clarify the prognostic relevance of ASXL1 and SETBP1 mutations, among others, in World Health Organization-defined chronic myelomonocytic leukemia (CMML) and its added value to the Mayo prognostic model. In univariate analysis, survival was adversely affected by ASXL1 (nonsense and frameshift) but not SETBP1 mutations. In multivariable analysis, ASXL1 mutations, absolute monocyte count > 10 x 10(9)/l, hemoglobin <10 g/dl, platelets <100 x 10(9)/l and circulating immature myeloid cells were independently predictive of shortened survival: hazard ratio (95% confidence interval (CI)) values were 1.5 (1.1-2.0), 2.2 (1.6-3.1), 2.0 (1.6-2.6), 1.5 (1.2-1.9) and 2.0 (1.4-2.7), respectively. A regression coefficient-based prognostic model based on these five risk factors delineated high (>= 3 risk factors; HR 6.2, 95% CI 3.7-10.4) intermediate-2 (2 risk factors; HR 3.4, 95% CI 2.0-5.6) intermediate-1 (one risk factor; HR 1.9, 95% CI 1.1-3.3) and low (no risk factors) risk categories with median survivals of 16, 31, 59 and 97 months, respectively. Neither ASXL1 nor SETBP1 mutations predicted leukemic transformation. The current study confirms the independent prognostic value of nonsense/frameshift ASXL1 mutations in CMML and signifies its added value to the Mayo prognostic model, as had been shown previously in the French consortium model.

引用

页码：2206 / 2212

页数：7

共 33 条

[1] Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms [J].

Abdel-Wahab, O. ;

Pardanani, A. ;

Patel, J. ;

Wadleigh, M. ;

Lasho, T. ;

Heguy, A. ;

Beran, M. ;

Gilliland, D. G. ;

Levine, R. L. ;

Tefferi, A. .

LEUKEMIA, 2011, 25 (07) :1200-1202

[2] The most commonly reported variant in ASXL1 (c.1934dupG;p.Gly646TrpfsX12) is not a somatic alteration [J].

Abdel-Wahab, O. ;

Kilpivaara, O. ;

Patel, J. ;

Busque, L. ;

Levine, R. L. .

LEUKEMIA, 2010, 24 (09) :1656-1657

[3] Clinical Effect of Point Mutations in Myelodysplastic Syndromes [J].

Bejar, Rafael ;

Stevenson, Kristen ;

Abdel-Wahab, Omar ;

Galili, Naomi ;

Nilsson, Bjoern ;

Garcia-Manero, Guillermo ;

Kantarjian, Hagop ;

Raza, Azra ;

Levine, Ross L. ;

Neuberg, Donna ;

Ebert, Benjamin L. .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (26) :2496-2506

[4] Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia [J].

Boultwood, J. ;

Perry, J. ;

Pellagatti, A. ;

Fernandez-Mercado, M. ;

Fernandez-Santamaria, C. ;

Calasanz, M. J. ;

Larrayoz, M. J. ;

Garcia-Delgado, M. ;

Giagounidis, A. ;

Malcovati, L. ;

Della Porta, M. G. ;

Jadersten, M. ;

Killick, S. ;

Hellstrom-Lindberg, E. ;

Cazzola, M. ;

Wainscoat, J. S. .

LEUKEMIA, 2010, 24 (05) :1062-1065

[5] Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias [J].

Carbuccia, N. ;

Trouplin, V. ;

Gelsi-Boyer, V. ;

Murati, A. ;

Rocquain, J. ;

Adelaide, J. ;

Olschwang, S. ;

Xerri, L. ;

Vey, N. ;

Chaffanet, M. ;

Birnbaum, D. ;

Mozziconacci, M. J. .

LEUKEMIA, 2010, 24 (02) :469-473

[6] Mutations of ASXL1 gene in myeloproliferative neoplasms [J].

Carbuccia, N. ;

Murati, A. ;

Trouplin, V. ;

Brecqueville, M. ;

Adelaide, J. ;

Rey, J. ;

Vainchenker, W. ;

Bernard, O. A. ;

Chaffanet, M. ;

Vey, N. ;

Birnbaum, D. ;

Mozziconacci, M. J. .

LEUKEMIA, 2009, 23 (11) :2183-2186

[7] ASXL1 but Not TET2 Mutations Adversely Impact Overall Survival of Patients Suffering Systemic Mastocytosis with Associated Clonal Hematologic Non-Mast-Cell Diseases [J].

Damaj, Gandhi ;

Joris, Magalie ;

Chandesris, Olivia ;

Hanssens, Katia ;

Soucie, Erinn ;

Canioni, Danielle ;

Kolb, Brigitte ;

Durieu, Isabelle ;

Gyan, Emanuel ;

Livideanu, Cristina ;

Cheze, Stephane ;

Diouf, Momar ;

Garidi, Reda ;

Georgin-Lavialle, Sophie ;

Asnafi, Vahid ;

Lhermitte, Ludovic ;

Lavigne, Christian ;

Launay, David ;

Arock, Michel ;

Lortholary, Olivier ;

Dubreuil, Patrice ;

Hermine, Olivier .

PLOS ONE, 2014, 9 (01)

[8] SETBP1 mutations in 658 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia and secondary acute myeloid leukemias [J].

Damm, F. ;

Itzykson, R. ;

Kosmider, O. ;

Droin, N. ;

Renneville, A. ;

Chesnais, V. ;

Gelsi-Boyer, V. ;

de Botton, S. ;

Vey, N. ;

Preudhomme, C. ;

Clavert, A. ;

Delabesse, E. ;

Park, S. ;

Birnbaum, D. ;

Fontenay, M. ;

Bernard, O. A. ;

Solary, E. .

LEUKEMIA, 2013, 27 (06) :1401-1403

[9] Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases [J].

Gelsi-Boyer, Veronique ;

Brecqueville, Mandy ;

Devillier, Raynier ;

Murati, Anne ;

Mozziconacci, Marie-Joelle ;

Birnbaum, Daniel .

JOURNAL OF HEMATOLOGY & ONCOLOGY, 2012, 5

[10] Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia [J].

Gelsi-Boyer, Veronique ;

Trouplin, Virginie ;

Adelaide, Jose ;

Bonansea, Julien ;

Cervera, Nathalie ;

Carbuccia, Nadine ;

Lagarde, Arnaud ;

Prebet, Thomas ;

Nezri, Meyer ;

Sainty, Danielle ;

Olschwang, Sylviane ;

Xerri, Luc ;

Chaffanet, Max ;

Mozziconacci, Marie-Joelle ;

Vey, Norbert ;

Birnbaum, Daniel .

BRITISH JOURNAL OF HAEMATOLOGY, 2009, 145 (06) :788-800

← 1 2 3 4 →