Chronic Lymphocytic Leukemia (CLL) 

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CLL is the most common adult leukemia in western countries characterized by the accumulation of small, mature-appearing neoplastic lymphocytes in the blood, marrow and secondary lymphoid tissues (Owen, 2018​). The median age at diagnosis is 70 years, with a male predominance (1.3 Male : 1 Female) in all ethnic subgroups (Bosch, 2019). Observe the visual differences between a CLL cell and a normal B lymphocyte cell above, thanks to the beautiful electron microscopy photos taken by our senior research technician, Eileen McMillan-Ward. 

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This chronic lymphoproliferative malignancy disorder is clinically diagnosed by the presence of > 5x10^9 clonal CD5+ CD23+ CD19+ and CD20+ B lymphocyte cells per liter of peripheral blood for more than 3 months, or the prevalent presence of its non-leukemic variant, known as small lymphocytic lymphoma (SLL) (Bosch, 2019). In most diagnosed cases, CLL can result in lymphocytosis, leukaemia cell infiltration of the marrow, lymphadenopathy, splenomegaly, and death if left untreated. Due to its evolving genetic variability, refractory potential, and higher chances of being asymptomatic in most diagnosed patients, CLL remains to be a prevalent incurable disease around the world.

 

Genetic factors contributing to the development of CLL in patients can be distinguished based on the mutational status of their immunoglobulin heavy-chain variable region genes (IGHV), and the chromosomal alterations present in the patients genetic material (For Example: del(13q), del(11q), trisomy 21, del(17q), del(8q)) (Ferrer, 2018​). Due to its heterogeneous clinical course, scientists were able to develop two clinical staging systems, Rai and Binet classifications that aid in speeding up the process of diagnosing CLL in patients at an earlier stage of its prognosis (Owen, 2018). Although CLL is currently deemed incurable, current treatment options focus on targeting and inhibiting specific metabolic pathways (BCR, and Apoptosis) using a combination of chemotherapy drug agents such as Venetoclax (Bcl-2 inhibitor), and Ibrutinib (BTK inhibitor) in hopes of finding a cure to this blood disease (Ferrer, 2018).  

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CLL Research in Dr. Versha Banerji's Lab

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Dr. Versha Banerji is the co-lead of the CLL Clinic at CCMB that currently follows a large (~1100) cohort of CLL patients to implement novel medications such as Ibrutinib to report unknown toxicities along with the impact on bioenergetics ex vivo. Currently, Dr. Versha Banerji's team focuses on investigating the roles of metabolism in CLL using patients’ samples processed in the tumor bank. In some of their work they found that cells containing a prognostic biomarker ZAP 70+ is more metabolically active than ZAP 70 - or normal B lymphocytes, and that ibrutinib or NAMPT inhibition decreases the ZAP 70 + bioenergetics profiles of CLL cells. The lab is currently looking at various drug combination therapies that target and disrupt mitochondrial function and metabolism.  

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CLL Webinar

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