Genomic and Clinicopathologic Features of Primary Myelofibrosis With Isolated 13q Deletion

Background: Primary myelofibrosis (PMF) is a rare myeloproliferative stem cell disorder. The genomic features in PMF are poorly understood. Characterization of genomic alternations in PMF helps to determine their association with clinicopathologic features for further therapeutic implications.

Patients and methods: In this retrospective study, we investigated genomic changes using array-based comparative genomic hybridization (aCGH) in 17 PMF patients with isolated del(13q) and confirmed our aCGH findings with quantitative polymerase chain reaction (PCR) assay. We also compared the clinicopathologic features of patients with del(13q) (n = 17) with those of patients with a normal karyotype (NK) (n = 26).

Results: Clinicopathologically, del(13q) PMF patients had significantly higher blast counts (P = .03) than did NK patients, who had significantly higher marrow cellularity (P = .02). The degree of bone marrow fibrosis of PMF-3 was higher in the del(13q) group than in the NK group. Splenomegaly was present significantly more often in the del(13q) PMF group than in the NK group (P = .03). Genomically, the Janus Kinase 2 V617F mutation was observed less often in del(13q) PMF patients (P = .07). The common deleted region in del(13q) was confined to 13q13-13q14.3 according to G-band karyotyping, demonstrating a minimal deleted region (MDR) of 15.323 Mb, identified using aCGH. The tumor suppressor genes, Retinoblastoma, Forkhead box protein O1, and Succinyl -CoA ligase [ADP-forming] subunit beta in the MDR were deleted, confirmed using real-time PCR to confirm our aCGH findings.

Conclusion: Accurate molecular characterization of del(13q) in PMF using aCGH and quantitative PCR provided further insight to define the MDR and analyze the genomic changes in del(13q) PMF patients.