Research Projects

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDs) are clonal disorders characterized by abnormal proliferation of blasts/myeloid precursors. Recent molecular markers have been identified to categorize cases into various risk categories, with next-generation sequencing (NGs) playing a significant role in understanding disease biology. A new subclass,'myeloid neoplasms with germline predisposition (MNGP), has been incorporated into the 2017 World Health Organization (WHO) classification of hematopoietic neoplasms. This subclass has clinical implications, including identifying hereditary predisposition, tailoring chemotherapeutic regimens, selecting donors for hematopoietic stem cell transplantation, and providing timely genetic counseling. The incidence of MNGPs has increased from 5-6% to 12-13% in AML/MDs, with newer germline variants being added to expand this category. However, differences in clinical behavior, such as incomplete penetrance and variable age of presentation, suggest that the presence of a germline hit alone may not be sufficient for AML/MDs development. An additional 'hit' in the form of acquisition of somatic variants may be necessary for a transformation to a full-blown disease. Understanding the interaction between germline and somatic variants can help explain the disease pathobiology. Due to lack of awareness and routine screening of laboratory hematological testing in the general population, early identification is often missed. This study aims to identify germline variants using targeted-panel-based NGs testing in an unselected cohort of AML/MDs cases, aiming to understand the gaps in the genetics of this disease.