Component

Methotrexate sensitivity in human hematopoietic cancer cells

Context-specific entity; species, compartment and exposure are stated on each claim.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. CRISPR depletion of AMDHD1 reduced methotrexate sensitivity in the tested human cancer cells.

    Human imidazolonepropionase / AMDHD1 → Methotrexate sensitivity in human hematopoietic cancer cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human hematopoietic cancer-cell CRISPR experiments.
    limitations
    Enzyme depletion is different from lowering dietary histidine. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    An upstream histidine-breakdown step also changed drug sensitivity.
    primary_references
    Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 170–176

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human hematopoietic cancer-cell CRISPR experiments. · source_derived_draft · unverified_draft

    ## histidine-amdhd-loss-mtx An upstream histidine-breakdown step also changed drug sensitivity. CRISPR depletion of AMDHD1 reduced methotrexate sensitivity in the tested human cancer cells. Model: Human hematopoietic cancer-cell CRISPR experiments. Limitations: Enzyme depletion is different from lowering dietary histidine. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2 Evidence access: Primary full text Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    Complete structured claim and evidence

  2. CRISPR depletion of FTCD reduced methotrexate sensitivity in HEL, Ramos and LAMA84 cells; an sgRNA-resistant murine Ftcd construct restored sensitivity in the rescue experiment.

    Human formimidoyltransferase cyclodeaminase / FTCD → Methotrexate sensitivity in human hematopoietic cancer cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human cancer lines, CRISPR/RNAi and mouse-cDNA rescue.
    limitations
    Drug-exposed culture and cross-species rescue; not evidence that histidine is universally harmful or beneficial. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    Removing this histidine-processing step made the tested cancer cells less sensitive to the drug.
    primary_references
    Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 146–152

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer lines, CRISPR/RNAi and mouse-cDNA rescue. · source_derived_draft · unverified_draft

    ## histidine-ftcd-loss-mtx Removing this histidine-processing step made the tested cancer cells less sensitive to the drug. CRISPR depletion of FTCD reduced methotrexate sensitivity in HEL, Ramos and LAMA84 cells; an sgRNA-resistant murine Ftcd construct restored sensitivity in the rescue experiment. Model: Human cancer lines, CRISPR/RNAi and mouse-cDNA rescue. Limitations: Drug-exposed culture and cross-species rescue; not evidence that histidine is universally harmful or beneficial. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2 Evidence access: Primary full text Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    Complete structured claim and evidence

  3. CRISPR depletion of HAL reduced methotrexate sensitivity in the tested human cancer cells.

    Human histidine ammonia-lyase / HAL → Methotrexate sensitivity in human hematopoietic cancer cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human hematopoietic cancer-cell CRISPR experiments.
    limitations
    Enzyme depletion is different from lowering dietary histidine. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    An upstream histidine-breakdown step also changed drug sensitivity.
    primary_references
    Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 162–168

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human hematopoietic cancer-cell CRISPR experiments. · source_derived_draft · unverified_draft

    ## histidine-hal-loss-mtx An upstream histidine-breakdown step also changed drug sensitivity. CRISPR depletion of HAL reduced methotrexate sensitivity in the tested human cancer cells. Model: Human hematopoietic cancer-cell CRISPR experiments. Limitations: Enzyme depletion is different from lowering dietary histidine. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2 Evidence access: Primary full text Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards