Myeloid switch of B-cell precursor ALL subtypes

Ester Mejstříková, PhD, and Michaela Nováková, PhD, Second Faculty of Medicine, Charles University, Prague, Czech Republic, discuss a phenomenon, firstly described in 2005, in which a pediatric B-cell precursor acute lymphoblastic leukemia (ALL) subtype switches phenotype towards the monocytic lineage. The investigators observed that the monocytic switch is accompanied by the gradual loss of CD19. A better understanding of the subtypes prone to switch is increasingly important, especially as anti-CD19 therapies are introduced in the treatment protocols and the determination of minimal residual disease (MRD) by flow cytometry (FC) relies on B-cell markers. In a recent study, using exome and RNA sequencing, the monocytic switch correlated positively with three genetic subtypes: rearranged DUX4r, rearranged ZNF384, and PAX5-P80R mutation. Additionally, an important discordance between FC and PCR-determined MRD was found on day 15 in patients with mutated PAX5-P80R. On day 33, the MRD discordance was observed in all three subtypes. This interview took place during the 2021 European School of Hematology (ESH) 2nd Translational Research Conference on Acute Lymphoblastic Leukemia.