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Peer-reviewedCC BYCommunications Biology

Choline-dependent methionine metabolism supports leukemia progression

  • Nirmalya Saha1
  • Lauren Lachowski1
  • Franchesca Franzen1
  • Sydney Alibeckoff2
  • Victor Vitvitsky2
  • Roshan Kumar2
  • Melanie Hutchings3
  • Malathi Kandarpa4
  • Hsiangyu Hu1
  • James Ropa5
  • Marisa J. L. Aitken4
  • Mark Y. Chiang6
7 more authors
  • Li Zhang7
  • Costas A. Lyssiotis7
  • Shannon A. Carty6
  • Moshe Talpaz4
  • Smiti Vaid Gupta3
  • Ruma Banerjee2
  • Andrew G. Muntean1
7 affiliations
  1. 1Department of Pathology, University of Michigan
  2. 2Department of Biological Chemistry, University of Michigan
  3. 3Department of Nutrition and Food Science, Wayne State University
  4. 4Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan School of Medicine and Comprehensive Cancer Center
  5. 5Indiana University School of Medicine
  6. 6Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan
  7. 7Department of Molecular & Integrative Physiology, University of Michigan
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Abstract

Tumor cells must occupy and thrive in a competitive microenvironment marked by limited metabolites, including essential amino acids like methionine. Using a leukemia suppression model and CRISPR screening, we found that the choline transporter SLC44A1 is overexpressed in leukemia patients and impacts leukemogenesis. Choline is an important nutrient for membrane synthesis and less commonly contributes to the methionine cycle. A metabolic analysis demonstrated that metabolites of the methionine pathway are significantly elevated in leukemic cells. Surprisingly, dietary restriction of methionine accelerated leukemogenesis in vivo. Choline can serve as an alternative source for methionine via the enzymatic activity of CHDH and BHMT. Under restrictive methionine conditions, BHMT and CHDH are significantly upregulated. In vivo, BHMT and CHDH are necessary for leukemia progression where they utilize choline as an alternative source to satisfy increased methionine demand. This pathway represents a vulnerability in cancer cells that may be exploited for therapeutic intervention.

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Cite

BibTeXRIS
BibTeX
@article{saha2026cholinedependent,
  title = {{Choline-dependent methionine metabolism supports leukemia progression}},
  author = {Nirmalya Saha and Lauren Lachowski and Franchesca Franzen and Sydney Alibeckoff and Victor Vitvitsky and Roshan Kumar and Melanie Hutchings and Malathi Kandarpa and Hsiangyu Hu and James Ropa and Marisa J. L. Aitken and Mark Y. Chiang and Li Zhang and Costas A. Lyssiotis and Shannon A. Carty and Moshe Talpaz and Smiti Vaid Gupta and Ruma Banerjee and Andrew G. Muntean},
  journal = {Communications Biology},
  year = {2026},
  month = jul,
  doi = {10.1038/s42003-026-10598-x},
  url = {https://doi.org/10.1038/s42003-026-10598-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Choline-dependent methionine metabolism supports leukemia progression
AU  - Nirmalya Saha
AU  - Lauren Lachowski
AU  - Franchesca Franzen
AU  - Sydney Alibeckoff
AU  - Victor Vitvitsky
AU  - Roshan Kumar
AU  - Melanie Hutchings
AU  - Malathi Kandarpa
AU  - Hsiangyu Hu
AU  - James Ropa
AU  - Marisa J. L. Aitken
AU  - Mark Y. Chiang
AU  - Li Zhang
AU  - Costas A. Lyssiotis
AU  - Shannon A. Carty
AU  - Moshe Talpaz
AU  - Smiti Vaid Gupta
AU  - Ruma Banerjee
AU  - Andrew G. Muntean
PY  - 2026
DA  - 2026/07/01
JO  - Communications Biology
DO  - 10.1038/s42003-026-10598-x
UR  - https://doi.org/10.1038/s42003-026-10598-x
AB  - Tumor cells must occupy and thrive in a competitive microenvironment marked by limited metabolites, including essential amino acids like methionine. Using a leukemia suppression model and CRISPR screening, we found that the choline transporter SLC44A1 is overexpressed in leukemia patients and impacts leukemogenesis. Choline is an important nutrient for membrane synthesis and less commonly contributes to the methionine cycle. A metabolic analysis demonstrated that metabolites of the methionine pathway are significantly elevated in leukemic cells. Surprisingly, dietary restriction of methionine accelerated leukemogenesis in vivo. Choline can serve as an alternative source for methionine via the enzymatic activity of CHDH and BHMT. Under restrictive methionine conditions, BHMT and CHDH are significantly upregulated. In vivo, BHMT and CHDH are necessary for leukemia progression where they utilize choline as an alternative source to satisfy increased methionine demand. This pathway represents a vulnerability in cancer cells that may be exploited for therapeutic intervention.
SN  - 2399-3642
ER  -