Evaluation of transcriptional profile during progression from Ph-negative myeloproliferative neoplasms to acute myeloid leukemia

• Grant number: 24/15250-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Tathiane Maistro Malta Pereira
• Grantee: Enzo Marques Panepucci
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Myeloid leukemias encompass a variety of hematological disorders characterized by the abnormal accumulation of myeloid cells in the bone marrow and circulation. These disorders are divided into two main forms: Myeloproliferative Neoplasms (MPNs) and Acute Myeloid Leukemia (AML).In MPNs, there is an excessive proliferation of mature and precursor myeloid cells, with generally slow and less aggressive progression. Symptoms may take time to appear, and therapies are generally more successful. In contrast, in AML, there is a failure in the maturation of myeloid cells, resulting in rapid disease progression and severe symptoms, requiring more invasive treatments that are less successful.The chromosomal translocation that creates the Philadelphia chromosome (Ph), resulting in the formation of the BCR-ABL1 chimeric gene, promotes uncontrolled cell proliferation and is important for separating two groups of MPNs: Ph+ MPNs, represented by Chronic Myeloid Leukemia (CML), and Ph- MPNs, represented by Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis, which, like CML, can evolve into AML. This transition is critical, with studies identifying various genetic alterations associated with it.Understanding the progression of MPNs to AML is crucial for identifying underlying mechanisms and facilitating early diagnosis, as well as therapeutic strategies. This study aims to identify gene expression changes in mononuclear cells from MPN patients before and after progression to AML.