Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases.
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 ∼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.
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.
Laura
L
Palomo
Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain.
Blanca
B
Xicoy
Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain.
Olga
O
Garcia
MDS Research Group, Institut De Recerca Contra La Leucèmia Josep Carreras, ICO-Hospital Germans Trias I Pujol, Universitat Autònoma De Barcelona, Badalona, Spain.
Mar
M
Mallo
MDS Research Group, Institut De Recerca Contra La Leucèmia Josep Carreras, ICO-Hospital Germans Trias I Pujol, Universitat Autònoma De Barcelona, Badalona, Spain.
Vera
V
Ademà
Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain.
Marta
M
Cabezón
Hematology Service, ICO-Hospital Duran I Reynals, Barcelona, Spain.
Montse
M
Arnan
Hematology Service, ICO-Hospital Duran I Reynals, Barcelona, Spain.
Helena
H
Pomares
CIMA LAB Diagnostics, Department of Biochemistry and Genetics, University of Navarra, Instituto De Investigación Sanitaria De Navarra, Pamplona, Spain.
María
M
José Larrayoz
CIMA LAB Diagnostics, Department of Biochemistry and Genetics, University of Navarra, Instituto De Investigación Sanitaria De Navarra, Pamplona, Spain.
María
M
José Calasanz
Department of Translational Hematology and Oncology Research, Taussing Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
Jaroslaw P
JP
Maciejewski
Department of Translational Hematology and Oncology Research, Taussing Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
Dayong
D
Huang
Division of Hematology, Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taiwan City, Taiwan.
Lee-Yung
LY
Shih
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Seishi
S
Ogawa
Hematology Department, Hospital Universitario La Fe, Valencia, Spain.
Jose
J
Cervera
Hematology Department, Hospital Universitario La Fe, Valencia, Spain.
Esperanza
E
Such
Hematology Service, ICO Girona Hospital Josep Trueta, Girona, Spain.
Rosa
R
Coll
Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain.
Javier
J
Grau
MDS Research Group, Institut De Recerca Contra La Leucèmia Josep Carreras, ICO-Hospital Germans Trias I Pujol, Universitat Autònoma De Barcelona, Badalona, Spain.
Francesc
F
Solé
Hematology Service, ICO-Hospital Germans Trias I Pujol, Institut De Recerca Contra La Leucèmia Josep Carreras, Universitat Autònoma De Barcelona, Badalona, Spain.
Lurdes
L
Zamora
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D004247:DNA / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D007621:Karyotyping; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016019:Survival Analysis
D004247:DNA