1. Flow cytometric expression of Bcl-2, Mcl-1, and their ratios correlates with primary and secondary cytogenetic changes and their combinations in multiple myeloma.
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Singla, Shelly, Sreedharanunni, Sreejesh, Singh, Archana, Singh, Charanpreet, Bose, Parveen, Kumar, Arun, Balakrishnan, Anand, Jain, Arihant, Khadwal, Alka, Lad, Deepesh, Prakash, Gaurav, Sharma, Praveen, Mallik, Nabhajit, Sachdeva, Man Updesh Singh, Das, Reena, and Malhotra, Pankaj
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MULTIPLE myeloma , *BONE marrow , *FLOW cytometry , *CYTOGENETICS , *BIOMARKERS - Abstract
Response to BH3 mimetics in multiple myeloma (MM) correlates with
CCND1 -rearrangement or expression of anti-apoptotic molecules, particularly Bcl-2 and Mcl-1. Our study investigates the relationship between cytogenetic abnormalities (CGAs) and intracellular Bcl-2 and Mcl-1 expression in myeloma plasma cells (MPCs) using flow cytometry (FCM). We measured median fluorescence intensity (MFI) of Bcl-2 and Mcl-1 in 163 bone marrow samples (143 MM, 20 controls) across various cell types. Both Bcl-2MFI and Mcl-1MFI were significantly higher in MPCs compared to other cells, with Bcl-2 MFI exceeding Mcl-1 MFI in MPCs. Bcl-2 expression peaked inCCND1 -rearranged cases, while Mcl-1 expression was highest in cases with 1q21 gain/amplification. Notably, 65–74% of cases with other CGAs exhibited moderate to strong Bcl-2 or Mcl-1 expression, indicating potential utility of BH3 mimetics in this group, while 25% showed dim to absent expression of one or both markers, suggesting potential futility in these patients. Our study highlights FCM’s potential for rapid Bcl-2 and Mcl-1 quantification, surpassing traditional methods. We propose that direct measurement of Bcl-2 and Mcl-1 expression in PCs by FCM, combined with cytogenetic characterization, could improve therapeutic decision-making regarding the use of BH3 mimetics in MM, potentially enhancing outcomes and overcoming resistance. [ABSTRACT FROM AUTHOR]- Published
- 2024
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