Hassan Bjeije, PhD

• Hematopoietic stem cells
• Leukemia stem cells
• Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS)
• Secondary Acute Myeloid Leukemia
• Genetic and epigenetic alterations
• Long and small non-coding RNAs

My research focuses on unraveling the molecular mechanisms driving the transformation of JAK2V617F mutant Myeloproliferative Neoplasms (MPNs) into post-MPN secondary Acute Myeloid Leukemia (sAML). This clonal evolution occurs in approximately 20% of Myelofibrosis (MF) patients and represents one of the most complex transformations in hematologic malignancies. Given that the genetic alterations promoting sAML differ significantly from de novo AML, current treatment options for post-MPN sAML patients are largely limited to standard chemotherapy. My research aims to identify novel therapeutic strategies by genetically targeting potential candidate oncogenes to induce synthetic lethality in JAK2V617F mutant MPN cells, offering new hope for these high-risk patients.

My research also focuses on understanding the effect of Jarid2 and Ezh2 loss of function on normal and neoplastic hematopoiesis. Polycomb repressive complex 2 (PRC2) is a well-characterized epigenetic modifier that can play contrasting behaviors in cancers and mutations in PRC2 components like EZH2 and JARID2 has been detected in MPN and post-MPN sAML cases. Jarid2 is a co-factor of PRC2 that recruits this complex to different sites in the genome to support its function of catalyzing the histone 3 lysine 27 tri-methylation (H3K27me3) mark which is associated with transcriptional repression. JARID2 genetic alterations occur specifically in post-MPN sAML patients, and our previous study showed that Jarid2 acts as a tumor suppressor in Myelofibrosis (MF). JARID2 gene expression is significantly downregulated in MF patients compared to Polycythemia Vera (PV), Essential Thrombocythemia (ET) and healthy blood cells. Additionally, our preliminary data implies Jarid2 exerts tumor suppressor function in Jak2V617F MPN independently from PRC2. These studies suggest that genetic alteration of JARID2 is an important event for MPN transformation. Therefore, understanding the molecular events that contribute to the genetic alterations of JARID2 in post-MPN sAML is necessary for the development of targeted therapies for this patient population, and represents the focus of this project.