Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases

Fecha de publicación: 01/02/2016

Autores de IIS La Fe

José Vicente Cervera Zamora

Autor
Esperanza Such Taboada

Autor

Participantes ajenos a IIS La Fe

Palomo L
Xicoy B
Garcia O
Mallo M
Ademà V
Cabezón M
Arnan M
Pomares H
José Larrayoz M
José Calasanz M
Maciejewski JP
Huang D
Shih LY
Ogawa S
Coll R
Grau J
Solé F
Zamora L

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

Abstract

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder with heterogeneous clinical, morphological and genetic characteristics. Clonal cytogenetic abnormalities are found in 20-30% of patients with CMML. Patients with low risk cytogenetic features (normal karyotype and isolated loss of Y chromosome) account for similar to 80% of CMML patients and often fall into the low risk categories of CMML prognostic scores. We hypothesized that single nucleotide polymorphism arrays (SNP-A) karyotyping could detect cryptic chromosomal alterations with prognostic impact in these subgroup of patients. SNP-A were performed at diagnosis in 128 CMML patients with low risk karyotypes or uninformative results for conventional G-banding cytogenetics (CC). Copy number alterations (CNAs) and regions of copy number neutral loss of heterozygosity (CNN-LOH) were detected in 67% of patients. Recurrent CNAs included gains in regions 8p12 and 21q22 as well as losses in 10q21.1 and 12p13.2. Interstitial CNN-LOHs were recurrently detected in the following regions: 4q24-4q35, 7q32.1-7q36.3, and 11q13.3-11q25. Statistical analysis showed that some of the alterations detected by SNP-A associated with the patients' outcome. A shortened overall survival (OS) and progression free survival (PFS) was observed in cases where the affected size of the genome (considering CNAs and CNN-LOHs) was >11 Mb. In addition, presence of interstitial CNN-LOH was predictive of poor OS. Presence of CNAs (>= 1) associated with poorer OS and PFS in the patients with myeloproliferative CMML. Overall, SNP-A analysis increased the diagnostic yield in patients with low risk cytogenetic features or uninformative CC and added prognostic value to this subset of patients. (C) 2015 Wiley Periodicals, Inc.

Datos de la publicación

ISSN/ISSNe:: 0361-8609, 1096-8652
Tipo:: Article
Páginas:: 185-192
DOI:: 10.1002/ajh.24227
Factor de Impacto:: 1,936 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Palomo L:: MDS Research Group, Institut De Recerca Contra La Leucèmia Josep Carreras, ICO-Hospital Germans Trias I Pujol, Universitat Autònoma De Barcelona, Badalona, Spain

Departament De Bioquímica I Biologia Molecular, Universitat Autònoma De Barcelona, Spain
Xicoy B:: Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain
Garcia O:: Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain
Mallo M:: MDS Research Group, Institut De Recerca Contra La Leucèmia Josep Carreras, ICO-Hospital Germans Trias I Pujol, Universitat Autònoma De Barcelona, Badalona, Spain
Ademà V:: MDS Research Group, Institut De Recerca Contra La Leucèmia Josep Carreras, ICO-Hospital Germans Trias I Pujol, Universitat Autònoma De Barcelona, Badalona, Spain
Cabezón M:: Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain
Arnan M:: Hematology Service, ICO-Hospital Duran I Reynals, Barcelona, Spain
Pomares H:: Hematology Service, ICO-Hospital Duran I Reynals, Barcelona, Spain
José Larrayoz M:: CIMA LAB Diagnostics, Department of Biochemistry and Genetics, University of Navarra, Instituto De Investigación Sanitaria De Navarra, Pamplona, Spain
José Calasanz M:: CIMA LAB Diagnostics, Department of Biochemistry and Genetics, University of Navarra, Instituto De Investigación Sanitaria De Navarra, Pamplona, Spain
Shih LY:: Division of Hematology, Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taiwan City, Taiwan
Ogawa S:: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Cervera J:: Hematology Department, Hospital Universitario La Fe, Valencia, Spain
Such E:: Hematology Department, Hospital Universitario La Fe, Valencia, Spain
Coll R:: Hematology Service, ICO Girona Hospital Josep Trueta, Girona, Spain
Grau J:: Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain
Solé F:: MDS Research Group, Institut De Recerca Contra La Leucèmia Josep Carreras, ICO-Hospital Germans Trias I Pujol, Universitat Autònoma De Barcelona, Badalona, Spain
Zamora L:: Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain