Pro106Leu MPL mutation is associated with thrombocytosis and a low risk of thrombosis, splenomegaly and marrow fibrosis

Abstract

The P106L mutation in the human myeloproliferative leukemia virus oncogene (MPL) was shown to be associated with hereditary thrombocythemia in Arabs. The clinical and bone marrow (BM) features of P106L mutation are unknown. Genetic databases at two tertiary hospitals in Saudi Arabia were searched to identify patients with the MPL P106L mutation. Clinical data were collected retrospectively and the BM aspirates and biopsies were independently reviewed by two hematopathologists. In total, 115 patients were included. Median age was 33 years of which 31 patients were pediatric and 65 were female. The mutation was homozygous in 87 patients. Thrombocytosis was documented in 107 patients, with a median platelet count of 667 × 10⁹/L. The homozygous genotype was associated with a higher platelet count. Thirty-three patients had an evaluable BM and clustering of megakaryocytes was observed in 30/33 patients. At the time of last follow-up, 114 patients were alive. The median follow-up was 7.8 years from the time of thrombocytosis. No patients developed disease progression to myelofibrosis. The P106L mutation was associated with marked thrombocytosis at a younger age and with a low risk of thrombosis, splenomegaly, and marrow fibrosis. The BM demonstrated normal or hypocellular marrow with megakaryocyte clusters.

Keywords:

• Familial thrombocythemia
• hereditary thrombocytosis
• MPL

Acknowledgements

The authors would like to acknowledge May-Ann Mendoza and Rania Jaha from KAIMRC, and all who contributed to the current study, including the patients. This study was also supported by KAIMRC and the College of Medicine Research Centre, Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia. The authors would like to thank and acknowledge the study statisticians Dr. Imad Abdulmajeed and Dr. Emad Masuadi.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authorship

Contribution: M. F. A., S. H. A., and A. M.A. helped in designing the study, collecting data, analysis, and writing the manuscript. All other authors contributed to collecting the data and reviewing and editing the manuscript. F.A.A and A.M.A contributed to the review of the bone marrow.

Additional information

Funding

The author(s) reported that the cost of the buccal/saliva genetic tests were covered by KAIMRC. Otherwise there is no funding associated with the work featured in this article.