Measurable residual disease in childhood B-cell acute lymphoblastic leukemia.

Abstract

In a recent report in Nature Cell Biology (2022. 24:242–52) Zhang and coworkers discuss comparative genetic and bio-chemical features of leukemia cells from children with B-cell acute lymphoblastic leukemia (ALL) obtained at diagnosis, in remission, and at relapse. 1 The authors analyzed large numbers of single-cell transcriptomes looking for dynamic changes and simultaneously, B-cell receptor sequences. They report that in contrast to leukemia cells at diagnosis, those at relapse shifted to a poorly-differentiated state. Changes in residual leukemia cells in remission were more complicated. Differential functional analyses highlighted activation of the hypoxia pathway in residual leukemia cells which correlated with drug resistance which was reversible with appropriate drug interventions in in vitro and in vivo models. The authors suggest this might be a therapy approach to eradicating measurable residual disease (MRD) in childhood B-cell ALL. This is a data dense article which requires understanding a machine learning algorithm. I suggest putting aside at least 5 hours to read and understand the text and supplement. I had to read it twice. This is not something to breeze through while texting on WeChat if you really want to understand the authors’ message and to critique it appropriately. First, a word on nomenclature. The authors use the term minimal residual disease . As John Goldman and I discussed several years ago the correct term is measurable residual disease . 2 Minimal is a subjective term; minimal to 1 person is not necessarily minimal to another. What we are considering is what can and cannot be measured in someone in complete histological remis- sion. (Another source of confusion; remissions are histological , not morphological . Morphology comes from the Greek μ&z. omicr; ρϕ which means form, structure or shape, not appear-ance). As an aside Morpheus was the Greek God of sleep and is the root of the drug name morphine. Lest you think I’m getting lost in semantics please recall the comment from George Orwell: