Summary
B-cell chronic lymphocytic leukemia (CLL) is a devastating, incurable B-cell malignancy and the most common form of leukemia in the Western hemisphere.
The research of Asish K. Ghosh, Ph.D., primarily focuses on CLL B-cell biology and its tumor microenvironment. He has a particular interest in identifying therapeutic and/or prognostic factors to better predict clinical progression of CLL and therapeutic outcome.
Recently, Dr. Ghosh and his team identified a novel receptor tyrosine kinase called Axl in CLL B-cells, which seems to play a critical role in CLL B-cell survival and apoptotic resistance. Interestingly, targeted inhibition of Axl induces massive cell death in primary CLL B-cells from CLL patients, suggesting it may have potential for future use as a therapeutic agent, either alone or in combination with the chemotherapeutic agents commonly being used to treat CLL.
Dr. Ghosh's laboratory has been working extensively to pursue the role of circulating microvesicles and exosomes in human malignancies, particularly CLL. His team has found a unique role of these extracellular vesicles — they function as a mediator of communication between the malignant tumor cells and cells at the distant tissues, such as bone marrow stroma.
Dr. Ghosh's research also focuses on further characterization of these circulating extracellular vesicles to be used as predictors of the clinical course and/or therapeutic outcome in CLL.
Focus areas
- In-depth study of the intracellular cell survival signaling pathways in CLL B-cells
- Implications of receptor tyrosine kinase-mediated signal transmission in cell survival and apoptosis resistance
- Targeting potential therapeutic component(s) in vitro and in vivo
- Testing of potential therapeutic agents in primary CLL cell culture systems
- Isolation and characterization of circulating microvesicles and exosomes from CLL plasma and purified CLL cells in vitro
- Functional interaction of circulating microvesicles and exosomes with the CLL bone marrow stromal cells to modulate the CLL tumor microenvironment
- Generation of microvesicles and exosomes as a result of interaction of the leukemic B-cells with other cell types in the CLL tumor microenvironment
- Studying aberrant intracellular signaling pathways in CLL bone marrow stromal cells
Significance to patient care
CLL accounts for about 11 percent of all newly diagnosed hematologic neoplasms. Given its chronic nature, there are estimated to be about 150,000 people in the U.S. who are living with CLL.
Importantly, clinicians are now able to more effectively treat progressive CLL, but treatment options are much less effective when a patient relapses. Since CLL patients are not routinely cured, clinicians are frequently faced with second-line therapies that have very inferior levels of deep clinical response and durability.
In addition, the current therapies for upfront treatments use agents that are either toxic to the marrow and/or difficult to use in older patients (those ages 65 and older). Therefore, any insights into drugs that have unique mechanism(s) of action and are nontoxic to the bone marrow are desperately needed.
Identification of unique therapeutic target in CLL requires more in-depth study of the leukemic B-cell biology and signaling pathways.