Molecular Profile of BCR-ABL1 Negative Myeloproliferative Neoplasm in a Moroccan Population

Myeloproliferative neoplasms (MPN) are associated with clonal hematopoiesis, genomic instability, hemostasis dysregulation, and immune response. Classic BCR-ABL1 negative myeloproliferative neoplasms (BCR-ABL1 negative MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are frequently associated with somatic abnormalities in JAK2, CALR, and MPL. Mutant clones induce an inflammatory immune response leading to immuno-thrombosis.

The aim of this research was to investigate JAK2/STAT5 mutations in 49 Moroccan patients and to study their correlation with demographic and hematological parameters.

Genomic DNA was isolated from peripheral blood samples, and JAK2V617F, JAK2 exon 12, CALR exon 9, and MPL exon 10 mutations were tested by qPCR, AS-PCR, and Sanger sequencing. Statistical analysis was performed using SPSS version 22.

Our results showed that 33 (67.35%) of our cohort was mutated for one of the investigated genes. JAK2V617F was detected in 25 cases, as well as two previously described CALR mutations: c.1092_1143del52 and c.1154_1155insTTGTC. Mutations in JAK2 exon 12 (c.1622G>A/C and c.1641+6T>C) were observed and in PV and ET. MPL substitution c.1544G>T was detected in two cases. Mutations in JAK2, CALR, and MPL were mutually exclusive and benign single nucleotide variations/polymorphisms (SNV/SNP) have been identified in CALR and JAK2. The JAK2-PV subgroup was associated with higher red mass cell, hemoglobin, and hematocrit levels. Higher platelet counts correlated with the JAK2-ET subgroup, while higher leukocyte and neutrophil counts were associated with the JAK2-PMF subgroup. Complete blood count revealed hyperleukocytosis accompanied by hyperplateletosis and a lower level of hemoglobin in CALR-ET mutated patients, compared to JAK2-ET mutated or triple negative-ET cases.

In conclusion, our study provides valuable insights into the prevalence and characteristics of JAK2, CALR, and MPL mutations in BCR-ABL1 negative MPNs in the Moroccan population, highlighting the importance of genetic characterization to optimize the clinical management of these diseases.