Lineage switch in leukemia and lymphoma: case reports and molecular and cellular mechanisms.
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Leukemias and lymphomas may occasionally show phenotypic lineage switch (LS) upon relapse with retention of genotypic signatures from the initial neoplasm (before and after switch). Such cases of LS are historically and currently associated with exceedingly poor prognosis in both pediatric and adult patients. Instances of LS are increasingly recognized, notably in B-cell acute lymphoblastic leukemia after immunotherapy. Hypotheses of LS have historically included transdifferentiation, dedifferentiation, and/or common progenitor cells. Experimental models have further clarified the changes in gene expression and epigenetic remodeling which drive lymphoid-myeloid reprogramming. Summarized herein are a collection of such findings, particularly regarding the most common type of LS in patients, namely B-cell neoplasms with conversion to myeloid phenotypes ("B-myeloid conversion"). Additionally, a review of the literature of pediatric and adult case reports is included to help represent the disease characteristics.