Objective: Chronic myeloproliferative neoplasms (MPNs) form a group of diseases characterized by clonal proliferation in all three cell lines of the bone marrow. “Philadelphia chromosome”-negative (Ph−) MPNs are primarily categorized into essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). The JAK-2 V617F mutation was found in 95–98% of PV patients and 50% of ET and PMF patients. Later, JAK2 exon-12 mutations in PV, MPL W515L/K and calreticulin mutations in PMF and ET were identified. Another mutation observed in MPN patients is the additional sex combs like 1 (ASXL1) gene mutation. This study investigated the frequency of ASXL1 gene mutations in 103 Ph− MPN patients and examined their impact on the disease’s clinical course and prognosis.
Materials and
Methods: A total of 103 Ph− MPN patients were included in the study. DNA sequence analysis was used to screen for ASXL1 gene mutations using blood count samples.

Results: ASXL1 gene mutations were detected in 6 patients (5.8%) in our cohort. Screening of the 12th exon of the ASXL1 gene revealed the most common mutation as c.1934dupG (p.g646TrpfsX12) and the second most frequent as c.1954G.a (p.G652S). The group with ASXL1 gene mutations showed higher rates of thrombosis. In our MPN group with an average follow-up duration of 4.1 years, non-hematologic cancer rates (solid tumors) were found to be considerably high (14.5%). 80% of these patients had the JAK-2 V617F mutation. Two patients with the JAK-2 V617F mutation also had the ASXL1 c.1954G.a (p.G652S) gene mutation.

Conclusion: In our cohort, the diagnosis of non-hematologic cancer following the use of hydroxyurea in five patients initially diagnosed with MPN suggests that hydroxyurea use might contribute to the development of non-hematologic cancer. On the other hand, the development of secondary cancer in two patients without hydroxyurea use post-MPN diagnosis indicates that factors other than hydroxyurea may also influence the development of non-hematologic cancers.