Diagnostic Approach and risk stratification of thrombocytosis: Integrating morphological, cytogenetic features and MPL gene mutation

Objectives: To evaluate the integration of clinical, morphological, cytogenetic features and MPL gene mutation analysis in Egyptian patients with clonal thrombocytosis and correlate these finding to patient’s outcome. Background: Thrombocytosis can be caused by either reactive or autonomous processes as a result of genetic alterations that affect signaling pathway through gain-of-function activity of MPL (myeloproliferative leukemia virus), Janus kinase 2 (JAK 2), calreticulin (CALR). Methods: This study was conducted on 60 Egyptian patients having clonal thrombocytosis attending to clinical pathology department, Ain Shams University Hospitals during the period from August 2020 to December 2021. Complete blood count, LDH level and MPL gene mutation by Real-time PCR were measured. Results: JAK2 gene mutation was more prevalent than MPL gene mutation in our study (40% and 8.3% respectively). MPL mutation has an aggressive nature than JAK2 mutation as evident by; older age (68.80± 2.28 vs 55.5 ± 8.28 accordingly), more thrombotic manifestation (100% vs 58.3%), higher platelets count (1221.4 ± 309.70 vs 879.38 ± 215.98) and poor response to therapy (0% of MPL positive patients achieved complete response to therapy vs 41.7% for JAK2 positive patients) but with no marked morphological difference regarding megakaryocytes morphology. Conclusion: MPL W515L/K mutations present in 10.3% in essential thrombocythemia Egyptian patients, included in our current study. MPL gene mutation has a bad prognostic effect. Moreover, presence of coexisting JAK2 & MPL mutation have a synergistic bad effect to be evaluated in further larger studies.