Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray
Norihiko Kawamata1, Seishi Ogawa, Go Yamamoto
1Hematology/Oncology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA 90048, USA. kawamatan@cshs.org
Experimental Hematology
|August 30, 2008
Summary
Genomic abnormalities are common in myeloproliferative disorders (MPD), particularly primary myelofibrosis (PMF). These include uniparental disomy and gene deletions, often occurring with JAK2 or MPL mutations.
Area of Science:
- Hematology
- Genetics
- Oncology
Background:
- Myeloproliferative disorders (MPD) are clonal hematopoietic stem cell neoplasms.
- Common MPDs include polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF).
- JAK2 mutations are frequent in MPD, but other genomic alterations remain understudied.
Purpose of the Study:
- To investigate genomic aberrations in patients with MPD.
- To identify novel genetic alterations associated with MPD subtypes.
Main Methods:
- Analysis of 43 MPD patients (10 PV, 17 ET, 16 PMF) using single-nucleotide polymorphism DNA microarray (SNP-chip).
Main Results:
- Genomic abnormalities were infrequent in ET.
- In PMF, deletions in RB1 (13q14) or NF1 (17q11) regions were observed in 4/16 patients, particularly those without JAK2 mutations.
- Homozygous JAK2V617F in PV cases showed uniparental disomy.
- 9p uniparental disomy was detected in 11 MPD patients (3 PV, 1 ET, 7 PMF).
- 1p uniparental disomy occurred in 1 PV and 3 PMF patients, associated with MPL mutations (Y591D, S204F, W515L).
Conclusions:
- Genomic abnormalities are prevalent in MPD, especially PMF.
- Common alterations include 9p and 1p uniparental disomy, and deletions of RB1 and NF1.
- These genetic changes are frequently associated with JAK2 or MPL mutations.
