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Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. While there are a number of well-recognized prognostic biomarkers at diagnosis, the most powerful independent prognostic factor is the response of the leukemia to induction chemotherapy (Campana and Pui: Blood 129 (2017) 1913-1918). Given the potential for machine learning to improve precision medicine, we tested its capacity to monitor disease in children undergoing ALL treatment. Diagnostic and on-treatment bone marrow samples were labeled with an ALL-discriminating antibody combination and analyzed by imaging flow cytometry. Ignoring the fluorescent markers and using only features extracted from bright-field and dark-field cell images, a deep learning model was able to identify ALL cells at an accuracy of >88%. This antibody-free, single cell method is cheap, quick, and could be adapted to a simple, laser-free cytometer to allow automated, point-of-care testing to detect slow early responders. Adaptation to other types of leukemia is feasible, which would revolutionize residual disease monitoring. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry., (© 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.)

Keywords: ambiguous lineage leukaemia; bilineal; monocytic; paediatric EN ambiguous lineage leukaemia bilineal monocytic paediatric e34 e39 6 01/28/22 20220201 NES 220201 Ambiguous lineage leukaemia (ALAL) is a rare sub-type of paediatric acute leukaemia. There are four main subgroups according to the lineage of differentiation, namely: (i) mixed phenotype acute leukaemia (MPAL), (ii) bilineal acute leukaemia, (iii) undifferentiated acute leukaemia, and (iv) acute leukaemia with early switch to a different lineage.1-4 MPAL accounts for 1-2% of paediatric leukaemia.3 The World Health Organization (WHO) classifications (2008 and 2016) have established strict criteria for diagnosis of MPAL, emphasising myeloperoxidase for myeloid lineage, cytoplasmic cluster of differentiation 3 (CD3) for T lineage, and CD19 and other B markers for B lineage.1,4 Flow cytometry has been pivotal in diagnosis, treatment response and minimal residual disease (MRD) assessment in MPAL. Acute lymphoblastic leukemia-like treatment regimen provides better response in mixed phenotype acute leukemia: a comparative study between adults and pediatric MPAL patients. A provisional diagnosis of AML with monocytic differentiation was considered and commenced on AML treatment as per UK national guidelines due to rising white blood cell counts (Table I). [Extracted from the article]

Deregulation of the Ras/Raf/MEK/extracellular signal-regulated kinase pathway is a common event in childhood acute lymphoblastic leukemia and is caused by point mutation, gene deletion, and chromosomal translocation of a vast array of gene types, highlighting its importance in leukemia biology. Pathway activation can be therapeutically exploited and may guide new therapies needed for relapsed acute lymphoblastic leukemia and other high risk subgroups. [ABSTRACT FROM AUTHOR]

Summary: We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary) recipients. Surprisingly, blasts representative of all of the different maturational stages were able to reconstitute and reestablish the complete leukemic phenotype in vivo. Sorted blast populations mirrored normal B precursor cells with transcription of a number of stage-appropriate genes. These observations inform a model for leukemia-propagating stem cells in childhood ALL. [Copyright &y& Elsevier]