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Editorials
Are meningeal cells also involved in specific homing of ALL cells into the CNS? Is adhesion-mediated chemoresistance of ALL cells in contact with meningeal cells simply a cause of decreased proliferation and therefore diminished vulner- ability to chemotherapeutic agents or is an active process involved (e.g., regulation of drug transporters)? Furthermore, it would be interesting to determine whether adhesion capacity of ALL cells to the CNS microenviron- ment could be used to improve CNS diagnostics. A recent report suggests that surface expression of a5-integrins on ALL cells is associated with the number of ALL cells in the cerebrospinal fluid detectable by diagnostic lumbar punc- ture.18 Finally, there is a need to consider that mobilizing dormant ALL cells by breaking adhesive bonds with meningeal cells may also confer potential risks. Re-awaken- ing leukemic cells may cause a resumption of proliferation and therefore overt CNS disease, an aspect which will have to be clarified in the future.
The recent study by Jonart et al. shapes a sharper image of the complex mechanisms of both CNS infiltration and CNS relapse, and may ultimately contribute to improved strategies for targeted treatment of CNS leukemia in ALL.
References
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18. Shah Scharff BFS, Modvig S, Thastrup M, et al. A comprehensive clinical study of integrins in acute lymphoblastic leukemia indicates a role of a6/CD49f in persistent minimal residual disease and a5 in the colonization of cerebrospinal fluid. Leuk Lymphoma. 2020 Feb 28;1-5. [Epub ahead of print]
BCL2 dependency in diffuse large B-cell lymphoma: it’s a family affair
Shannon M. Matulis and Lawrence H. Boise
Department of Hematology and Medical Oncology Emory School of Medicine and the Winship Cancer Institute, Emory University; Atlanta, GA, USA
E-mail: LAWRENCE H. BOISE - lboise@emory.edu doi:10.3324/haematol.2020.253591
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma, accounting for approximately 25% of all lym- phomas.1 DLBCL is highly heterogeneous, so responses to standard therapy, R-CHOP (rituximab plus cyclophos- phamide, doxorubicin, vincristine, and prednisone) are mixed.2 The response, as well as mechanisms of resist- ance to therapy, are associated with a cell’s apoptotic threshold.3 Therefore, determining the molecular basis for a tumor’s ability to survive can provide insights into drug resistance as well as opportunities for precision medicine. In this issue of Haematologica, Smith et al. demonstrate the
importance of the BCL2 family of anti-apoptotic proteins
BCL2, BCLXL, and MCL1 in the survival of DLBCL,
4 potentially revealing new treatment strategies.
Inappropriate activation of oncogenes can result in cell death through the activation of pro-apoptotic proteins of the BCL2 family. Therefore, to survive the transformation process, tumor cells become more dependent on their anti-apoptotic BCL2 proteins (e.g., BCL2, BCLXL, and MCL1) than their normal counterparts.5-7 This dependen- cy is the result of binding and neutralizing the pro-apop- totic family members (e.g., BIM, BAK, and BAX) and is often referred to as mitochondrial priming, as increased
haematologica | 2020; 105(8)
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