Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact

被引：49

作者：

Bacher, Ulrike ^{[1
]}

Haferlach, Torsten ^{[1
]}

Schnittger, Susanne ^{[1
]}

Zenger, Melanie ^{[1
]}

Meggendorfer, Manja ^{[1
]}

Jeromin, Sabine ^{[1
]}

Roller, Andreas ^{[1
]}

Grossmann, Vera ^{[1
]}

Krauth, Maria-Theresa ^{[1
,2
]}

Alpermann, Tamara ^{[1
]}

Kern, Wolfgang ^{[1
]}

Haferlach, Claudia ^{[1
]}

机构：

[1] Munich Leukemia Lab, D-81377 Munich, Germany

[2] Med Univ Vienna, Div Haematol & Haemostaseol, Dept Internal Med 1, Vienna, Austria

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2014年 / 164卷 / 06期

关键词：

U2AF1; mutation; myelodysplastic syndromes; SRSF2; cytogenetics; 20q deletion; ACUTE MYELOID-LEUKEMIA; SCORING SYSTEM; FLOW-CYTOMETRY; CHROMOSOME; 20Q; SYNDROMES MDS; MUTATIONS; MALIGNANCIES; EXPRESSION; SRSF2; ASXL1;

D O I：

10.1111/bjh.12710

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In patients with myelodysplastic syndromes (MDS), sole 20q deletion [del(20q)] is a recurrent favourable abnormality. We studied additional molecular and cytogenetic lesions and their prognostic impact in 305 MDS patients with del(20q) (229 males/76 females; 29-90years). All patients were investigated by cytomorphology and chromosome banding analysis (CBA), subsets by fluorescence in situ hybridization, molecular mutation screening, and array comparative genomic hybridization (aCGH). By aCGH (n=30), the minimal common deleted region (CDR) was flanked by PTPRT (20q13 center dot 11) and EYA2 (20q13 center dot 12). 210 (68 center dot 9%) patients had 'early MDS' without blast increase, 95 (31 center dot 1%) 'advanced' MDS with blast increase (5-19%). Additional chromosomal abnormalities (ACAs) were detected in 88/305 (28 center dot 9%) patients. Patients with advanced MDS more frequently had ACAs (P= 0 center dot 003) and had a higher mean number of ACAs (P=0 center dot 020) and of molecular mutations (P=0 center dot 060). Spliceosome mutations were frequent (U2AF1: n=31/155; 20 center dot 0%; SRSF2: n=31/159; 19 center dot 5%; SF3B1mut: n=8/159; 5 center dot 0%). ASXL1mut (25/153; 16 center dot 3%) were associated with advanced MDS (P=0 center dot 001). Presence of >= 3 ACAs (P=0 center dot 003) and ASXL1mut (P=0 center dot 002) were associated with worse 2-year survival. In conclusion, the cytogenetic subgroup of MDS with del(20q) has a good prognosis but may be further subclassified by additional cytogenetic and molecular lesions. U2AF1mut is overrepresented in MDS with del(20q), and ASXL1mut is prognostically adverse.

引用

页码：822 / 833

页数：12

共 41 条

[31] Coalesced Multicentric Analysis of 2,351 Patients With Myelodysplastic Syndromes Indicates an Underestimation of Poor-Risk Cytogenetics of Myelodysplastic Syndromes in the International Prognostic Scoring System [J].

Schanz, Julie ;

Steidl, Christian ;

Fonatsch, Christa ;

Pfeilstoecker, Michael ;

Noesslinger, Thomas ;

Tuechler, Heinz ;

Valent, Peter ;

Hildebrandt, Barbara ;

Giagounidis, Aristoteles ;

Aul, Carlo ;

Luebbert, Michael ;

Stauder, Reinhard ;

Krieger, Otto ;

Garcia-Manero, Guillermo ;

Kantarjian, Hagop ;

Germing, Ulrich ;

Haase, Detlef ;

Estey, Elihu .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (15) :1963-1970

[32] Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype [J].

Schnittger, S ;

Schoch, C ;

Kern, W ;

Mecucci, C ;

Tschulik, C ;

Martelli, MF ;

Haferlach, T ;

Hiddemann, W ;

Falini, B .

BLOOD, 2005, 106 (12) :3733-3739

[33] ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome [J].

Schnittger, S. ;

Eder, C. ;

Jeromin, S. ;

Alpermann, T. ;

Fasan, A. ;

Grossmann, V. ;

Kohlmann, A. ;

Illig, T. ;

Klopp, N. ;

Wichmann, H-E ;

Kreuzer, K-A ;

Schmid, C. ;

Staib, P. ;

Peceny, R. ;

Schmitz, N. ;

Kern, W. ;

Haferlach, C. ;

Haferlach, T. .

LEUKEMIA, 2013, 27 (01) :82-91

[34] Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia:: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease [J].

Schnittger, S ;

Schoch, C ;

Dugas, M ;

Kern, W ;

Staib, P ;

Wuchter, C ;

Löffler, H ;

Sauerland, CM ;

Serve, H ;

Büchner, T ;

Haferlach, T ;

Hiddemann, W .

BLOOD, 2002, 100 (01) :59-66

[35] Isoderivative chromosome 20 in bone marrow: three new cases [J].

Shetty, Shashirekba ;

Roland, Birgitte .

CANCER GENETICS AND CYTOGENETICS, 2008, 184 (01) :72-73

[36] Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes [J].

Thol, Felicitas ;

Kade, Sofia ;

Schlarmann, Carola ;

Loeffeld, Patrick ;

Morgan, Michael ;

Krauter, Juergen ;

Wlodarski, Marcin W. ;

Koelking, Britta ;

Wichmann, Martin ;

Goerlich, Kerstin ;

Goehring, Gudrun ;

Bug, Gesine ;

Ottmann, Oliver ;

Niemeyer, Charlotte M. ;

Hofmann, Wolf-Karsten ;

Schlegelberger, Brigitte ;

Ganser, Arnold ;

Heuser, Michael .

BLOOD, 2012, 119 (15) :3578-3584

[37] Prognostic Significance of ASXL1 Mutations in Patients With Myelodysplastic Syndromes [J].

Thol, Felicitas ;

Friesen, Inna ;

Damm, Frederik ;

Yun, Haiyang ;

Weissinger, Eva M. ;

Krauter, Juergen ;

Wagner, Katharina ;

Chaturvedi, Anuhar ;

Sharma, Amit ;

Wichmann, Martin ;

Goehring, Gudrun ;

Schumann, Christiane ;

Bug, Gesine ;

Ottmann, Oliver ;

Hofmann, Wolf-Karsten ;

Schlegelberger, Brigitte ;

Heuser, Michael ;

Ganser, Arnold .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (18) :2499-2506

[38] Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes [J].

van de Loosdrecht, Arjan A. ;

Alhan, Canan ;

Bene, Marie Christine ;

Della Porta, Matteo G. ;

Drager, Angelika M. ;

Feuillard, Jean ;

Font, Patricia ;

Germing, Ulrich ;

Haase, Detlef ;

Homburg, Christa H. ;

Ireland, Robin ;

Jansen, Joop H. ;

Kern, Wolfgang ;

Malcovati, Luca ;

Marvelde, Jeroen G. Te ;

Mufti, Ghulam J. ;

Ogata, Kiyoyuki ;

Orfao, Alberto ;

Ossenkoppele, Gert J. ;

Porwit, Anna ;

Preijers, Frank W. ;

Richards, Stephen J. ;

Schuurhuis, Gerrit Jan ;

Subira, Dolores ;

Valent, Peter ;

van der Velden, Vincent H. J. ;

Vyas, Paresh ;

Westra, August H. ;

de Witte, Theo M. ;

Wells, Denise A. ;

Loken, Michael R. ;

Westers, Theresia M. .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2009, 94 (08) :1124-1134

[39]

Weisser M, 2005, HAEMATOLOGICA, V90, P881

[40] Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group [J].

Westers, T. M. ;

Ireland, R. ;

Kern, W. ;

Alhan, C. ;

Balleisen, J. S. ;

Bettelheim, P. ;

Burbury, K. ;

Cullen, M. ;

Cutler, J. A. ;

Della Porta, M. G. ;

Drager, A. M. ;

Feuillard, J. ;

Font, P. ;

Germing, U. ;

Haase, D. ;

Johansson, U. ;

Kordasti, S. ;

Loken, M. R. ;

Malcovati, L. ;

te Marvelde, J. G. ;

Matarraz, S. ;

Milne, T. ;

Moshaver, B. ;

Mufti, G. J. ;

Ogata, K. ;

Orfao, A. ;

Porwit, A. ;

Psarra, K. ;

Richards, S. J. ;

Subira, D. ;

Tindell, V. ;

Vallespi, T. ;

Valent, P. ;

van der Velden, V. H. J. ;

de Witte, T. M. ;

Wells, D. A. ;

Zettl, F. ;

Bene, M. C. ;

van de Loosdrecht, A. A. .

LEUKEMIA, 2012, 26 (07) :1730-1741

← 1 2 3 4 5 →