b'Understanding Mechanisms Leading to B-Myeloid Lineage-Switching in CLL By LaTina EmersonCLEVELANDLineage-switching is a mechanism that can lead to treatment resistance in chronic lym- Unraveling the mechanisms underlying phocytic leukemia (CLL), and, though its a rare oc- B-myeloid lineage switching will lead currence, it can be fatal.to identification of effective specific The ability of CLL cells to convert to different cellpathway inhibitors to prevent and target types makes it challenging to treat this type of can- these uncommon, but fatal converted cer. CLL can occasionally transdifferentiate intomyeloid neoplasms.clonally related histiocytic sarcoma (a myeloid neo-plasm)oracutemyeloidleukemia(AML).These Chen Zhao, MD, PhDpatientsoftenpresentwithadvanceddiseaseand haveapoorprognosisbecauseofdifficultiesinof Pathology at the University of Iowa. He encoun-making a definitive diagnosis and lack of standardtered two cases where patients with with a long his-treatment. tory of CLL developed AML during treatment.A study published in the journal Blood AdvancesInvestigatingtheunderlyingmechanismsof examinedCLLtransdifferentiatingintoclonallyB-myeloidconversionwillcontributetoabetter related myeloid cells (histiocytic sarcoma or acuteunderstanding of therapy resistance. Almost all of myeloidleukemia).Thestudydemonstratesforthese cases occur post therapy. In general, patients the first time that CLL cells can dedifferentiate towith converted myeloid neoplasms have poor prog-myeloid cells. 1 nosis, Zhao wrote in an email. Our finding indicates that CLL cells can becomeThestudysmostimportantfindingisthat resistant to therapy through lineage switching, whichB-myeloid conversion is through dedifferentiation, renders the original therapy ineffective, Chen Zhao,then redifferentiation, processes. Converted myeloid MD,PhD,associateprofessorintheDepartmentneoplasmsandlymphoidneoplasmsareclonally-ofPathologyatCase WesternReserveUniversityrelated, Zhao explained in an email.in Cleveland, told U.S. Medicine. Cancer therapyUnraveling the mechanisms underlying B-myeloid resistance is associated with cancer cell heterogene- lineage switching will lead to identification of effec-ityandplasticity,whichfrequentlycorrelatewithtive specific pathway inhibitors to prevent and target moreaggressivephenotypesandpoorprognosis.these uncommon, but fatal converted myeloid neo-Patients with B cell neoplasms (lymphoma or leuke- plasms, Zhao wrote in an email. Prevention and mia) occasionally develop clonally-related myeloidtargetingB-myeloidconversioniscriticaltotreat neoplasms after treatment. Reports indicate that 2.9these patients. We are continuing to investigate the to 8% of patients with B-ALL had lineage switch- underlying molecular mechanisms to target cancer ing after treatment. How to target these convertedcell plasticity.myeloid neoplasms is largely unknown due to the1Dong Q, Xiu Y, Bossler A, Syrbu S, Wang H, Xue W, Zhao J, Li absence of good model systems to investigate theQ, Jin M, Wang L, Boyce B, Sakr H, Ansari MQ, Zhao C. CLL underlying process.dedifferentiation to clonally related myeloid cells. Blood Adv. 2020 The cases in the study were collected from ZhaosDec 22;4(24):6169-6174. doi: 10.1182/bloodadvances.2020002726. daily clinical service while working at the DepartmentPMID: 33351112; PMCID: PMC7756991.83'