Acute myeloid leukemia-driven IL-3-dependent upregulation of BCL2 in non-malignant hematopoietic stem and progenitor cells increases venetoclax-induced cytopenias

Dominic J Fowler-Shorten; Rebecca S Maynard; Katherine Hampton; Annalisa Altera; Matthew Markham; Martha Ehikioya; Edyta E Wojtowicz; Kristian M Bowles; Stuart A Rushworth; Charlotte Hellmich

doi:10.3324/haematol.2023.283944

Acute myeloid leukemia-driven IL-3-dependent upregulation of BCL2 in non-malignant hematopoietic stem and progenitor cells increases venetoclax-induced cytopenias

Haematologica. 2024 May 1;109(5):1576-1581. doi: 10.3324/haematol.2023.283944.

Affiliations

¹ Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ.
² Earlham Institute, Norwich Research Park, Norwich, NR4 7UH.
³ Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, United Kingdom; Department of Haematology, Norfolk and Norwich University Hospital NHS Trust, Colney Lane, Norwich, NR4 7UY.
⁴ Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ. s.rushworth@uea.ac.uk.
⁵ Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, United Kingdom; Department of Haematology, Norfolk and Norwich University Hospital NHS Trust, Colney Lane, Norwich, NR4 7UY. c.hellmich@uea.ac.uk.

No abstract available

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Bridged Bicyclo Compounds, Heterocyclic* / pharmacology
Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
Cytopenia
Hematopoietic Stem Cells* / drug effects
Hematopoietic Stem Cells* / metabolism
Humans
Interleukin-3* / metabolism
Leukemia, Myeloid, Acute* / drug therapy
Leukemia, Myeloid, Acute* / metabolism
Leukemia, Myeloid, Acute* / pathology
Proto-Oncogene Proteins c-bcl-2* / genetics
Proto-Oncogene Proteins c-bcl-2* / metabolism
Sulfonamides* / pharmacology
Up-Regulation / drug effects

Substances

venetoclax
Sulfonamides
Bridged Bicyclo Compounds, Heterocyclic
Proto-Oncogene Proteins c-bcl-2
Interleukin-3
BCL2 protein, human
Antineoplastic Agents
IL3 protein, human

Grants and funding

Funding: This work was supported by a Wellcome Trust Clinical Research Fellowship (220534/Z/20/Z) (to CH), the Medical Research Council project (MR/T02934X/1) (to SAR), a Sir Henry Welcome Postdoctoral Fellowship (213731/Z/18/Z) (to EEW), and the Biotechnology and Biological Sciences Research Council, part of UK Research and Innovation’s Core Capability (grant BB/CCG1720/1).