Hussein Abbas, MD, PhD
Assistant Professor, Department of Leukemia
University of Texas MD Anderson Cancer Center
Assistant Professor, Department of Genomic Medicine
University of Texas MD Anderson Cancer Center
Adjunct Assistant Professor
University of Texas School of Biomedical Informatics
Regular Member
University of Texas Graduate School of Biomedical Sciences
Research
Immune and Epigenetic Determinants of the Transformation of Myelodysplastic Syndrome with Deletion in Chromosome 7/7q to Acute Myeloid Leukemia
Summary
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are aggressive blood disorders that lead to a high risk of infections, anemia, and bleeding. One of the characteristics of these diseases is large changes in the genetic material leading to the acquisition of therapy-resistant features. One of those genetic changes is the loss of chromosome 7. MDS patients who have lost chromosome 7 are more likely to transform into an AML and have high resistance to any available therapies. It is still not clear how the loss in chromosome 7 aids in MDS transformation to AML and confers high therapy resistance states. Our preliminary data suggest that when cells lose chromosome 7, it influences the immune environment where MDS and AML cells reside and thus prevents the normal function of the immune system. Our proposed work aims at understanding how and why chromosome 7 loss generates such remodeling of the immune environment. We will leverage state-of-the-art tools that break down the bone marrow, where these cancer cells reside, into single-cell levels allowing for high-resolution analysis. Since this genetic abnormality occurs in almost one out of three AML/MDS patients, our study will provide major insights into how we can remodel the immune system to help in preventing MDS transformation into AML and will impact a large subset of patients.
Impact
The Leukemia Research Foundation grant has made a pivotal difference to our research and facilitated significant advancements in the understanding of T-cell dynamics in myeloid leukemia, specifically focusing on the deletion 7/7q anomaly, a genetic factor that has demonstrated a high level of resistance to therapeutic interventions. The critical insights gained through our investigation have broadened our knowledge of the immune landscape's contribution to myeloid neoplasms, disease progression, and therapy resistance. Notably, our research findings have revealed distinct inflammatory phenotypes and T cell states associated with del7/7q genetic abnormalities. This newfound understanding of the genetic abnormalities' unique inflammatory phenotype is relevant and novel in the field of blood cancer research.
Perhaps one of the most profound implications of our findings is the identification of a novel inflammatory pathway. This can be potentially targeted using an existing FDA-approved drug, an exciting prospect that we are actively pursuing in our ongoing research into myeloid neoplasms. Surprisingly, we did not observe an increase in checkpoint genes in our study, rather we identified a new dysfunctional signature associated with therapeutic resistance and disease progression. This finding, initially unexpected, has given us valuable direction for future research, providing a strong basis for multiple subsequent grant applications. Moreover, this new understanding of inflammation as a significant component in myeloid leukemia is now a central theme of our ongoing research. Our study's outcomes have already begun influencing the blood cancer research field, paving the way for future investigations and potential therapeutic strategies. The knowledge we've gained could play a crucial role in developing innovative immunotherapies aimed at manipulating T-cell behavior and reconstituting immune control to mitigate risk of therapy resistance and transformation.
The grant has been instrumental in propelling our research forward, enabling us to make significant contributions to the scientific community. We are excited about the potential our findings have to inform the development of more effective treatments for patients with del7/7q. We are committed to continuing our research efforts in this important area and look forward to sharing our future findings with the Leukemia Research Foundation and the generous donors.
Publication:
https://www.nature.com/articles/s42003-023-05120-6
MD Anderson Feature:
Leukemia Research Foundation grant
$93K awarded in 2022
Disease focus
Acute myeloid leukemia (AML)
Myelodysplastic syndromes (MDS)
Research focus
Causes/risk factors (MDS)