Poluben L., Chen S., Yuan X., Shumeiko O., Voznesensky O., Adam M., Fraenkel E., Rasnic R., Linial M., Klymenko S., Balk S. P., Fraenkel P. G


About the author:

Poluben L., Chen S., Yuan X., Shumeiko O., Voznesensky O., Adam M., Fraenkel E., Rasnic R., Linial M., Klymenko S., Balk S. P., Fraenkel P. G



Type of article:

Scentific article


In this study we aimed to identify the spectrum of affected genes in Ukrainian patients diagnosed with primary myelofibrosis (PMF). DNA samples were obtained from peripheral blood leukocytes of 30 Ukrainian PMF patients. Using Whole Exome Sequencing, we detected previously reported and unreported sequence variants considered as pathogenic or potentially pathogenic. Canonical mutations of usual MPN-driver genes were detected in 70% of PMF patients, including JAK2V617F – in 43.3%, MPLW515 – in 10% and CALRmutations (type 1-like and 2-like) – in 16.7% of patients. Also, a non-canonical MPLP222S variant was detected in one patient negative for these mutations. However, in cell culture assay, MPLP222S expression in Ba/F3 cells did not demonstrate differences in phosphorylation of JAK/STAT signaling proteins in response to TPO stimulation compared to MPLWT expression. Overall, more pathogenic and potentially pathogenic sequence variants were found among PMF patients negative for canonical mutations in three driver genes (JAK2, MPL andCALR), compared to patients, positive for one of these mutations. The mean numbers of variants were 5 (range: 4 – 7) versus 3.3 (range: 1 – 9), respectively (p = 0.03). The most frequently affected among Ukrainian PMF patients were genes ASXL1, PEG3, EZH2, ATM, U2AF1, andCDH23in addition to JAK2, MPL andCALR. Pathogenic or potentially pathogenic sequence variants of ASXL1and EZH2genes were identified in 23.3% and 16.7% of cases, respectively. Genes JARID2, RBBP8, RTEL1, SUZ12, BRCA2, LAMB4, NF1, RBM12B, RBM43, and RBP3 were recurrently affected in PMF patients who were also positive for usual mutations in three driver genes. Among PMF patients negative for usual mutations in three driver genes recurrently affected genes were DNMT3Aand TET2in addition to mentioned earlier, and some genetic variants were identified in RTEL1, SUZ12, CBL, CUX1, FLT3LGand UMODL1genes in single cases. Also, we identified several genes affected in single cases (KIT, SF3B1, GNAS) in PMF patients negative for canonical mutations in three driver genes which may be potential MPN drivers.


primary myelofibrosis, mutation, gene.


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Publication of the article:

«Bulletin of problems biology and medicine» Issue 4 Part 2 (147), 2018 year, 204-208 pages, index UDK 591.156:575.113:616-005.6:616.155.191