Molecular allelokaryotyping of T-cell prolymphocytic leukemia cells with high density single nucleotide polymorphism arrays identifies novel common genomic lesions and acquired uniparental disomy.
BACKGROUND
T-cell prolymphocytic leukemia is a rare aggressive lymphoproliferative disease with a mature T-cell phenotype and characteristic genomic lesions such as inv(14)(q11q34), t(14;14)(q11;q32) or t(X;14)(q28;q11), mutation of the ATM gene on chromosome 11 and secondary alterations such as deletions of chromosome 8p and duplications of 8q.


METHODS
We analyzed malignant cells from 18 patients with T-cell prolymphocytic leukemia using high density 250K single nucleotide polymorphism arrays and molecular allelokaryotyping to refine understanding of known alterations and identify new target genes.


RESULTS
Our analyses revealed that characteristic disruptions of chromosome 14 are frequently unbalanced. In the commonly deleted region on chromosome 11, we found recurrent microdeletions targeting the microRNA 34b/c and the transcription factors ETS1 and FLI1. On chromosome 8, we identified genes such as PLEKHA2, NBS1, NOV and MYST3 to be involved in breakpoints. New recurrent alterations were identified on chromosomes 5p, 12p, 13q, 17 and 22 with a common region of acquired uniparental disomy in four samples on chromosome 17q. Single nucleotide polymorphism array results were confirmed by direct sequencing and quantitative real-time polymerase chain reaction.


CONCLUSIONS
The first high density single nucleotide polymorphism array allelokaryotyping of T-cell prolymphocytic leukemia genomes added substantial new details about established alterations in this disease and moreover identified numerous new potential target genes in common breakpoints, deletions and regions of acquired uniparental disomy.
Nowak
Daniel
D
Division of Hematology and Oncology, Cedars Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. Daniel.Nowak@cshs.org
Le Toriellec
Emilie
E
Stern
Marc-Henri
MH
Kawamata
Norihiko
N
Akagi
Tadayuki
T
Dyer
Martin J
MJ
Hofmann
Wolf-Karsten
WK
Ogawa
Seishi
S
Koeffler
H Phillip
HP
D000483:Alleles; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D006801:Humans; D007621:Karyotyping; D015461:Leukemia, Prolymphocytic, T-Cell / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D024182:Uniparental Disomy