What question did this study set out to answer?

This research aims to investigate the role of PTPN11 mutations within the clonal hierarchy and immunophenotype of acute myeloid leukemia.

February 25, 2026JCI InsightOpen Access

Characterization of the clonal hierarchy and immunophenotype of PTPN11 mutations in acute myeloid leukemia

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Reveals PTPN11 mutations as initiating events in acute myeloid leukemia, indicating complex clonal dynamics.

This research aims to investigate the role of PTPN11 mutations within the clonal hierarchy and immunophenotype of acute myeloid leukemia.
Employed single-cell DNA sequencing to analyze mutations
Utilized murine models to study the role of PTPN11 in AML
Examined the diversity of myeloid cells and their differentiation stages
Analyzed cytokine responses from lineage-negative bone marrow cells after stimulation
PTPN11 mutations can serve as initiating events in AML alongside NPM1 mutations
Identified diverse myeloid cells with varying differentiation and few cells lacking leukemic mutations
Confirmed PTPN11's role as a codriver of AML in murine models with immune diversity
Bone marrow cells from mice showed a complete range of mature myeloid cells with altered cytokine responses

Fobare et al. (2026) studied this question.

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