How the order of mutations influences leukemia development

Impact of mutational order on molecular mechanisms of oncogenesis

NIH-funded research Icahn School of Medicine at Mount Sinai · NIH-11286793

Researchers change the order of cancer-driving mutations in human blood stem cells to learn how different sequences can lead to acute myeloid leukemia.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionIcahn School of Medicine at Mount Sinai NIH-funded
Lab location1 site (New York, United States)
Project IDNIH-11286793 on NIH RePORTER

What this research studies

Researchers at Mount Sinai will use CRISPR to introduce key leukemia mutations into human induced pluripotent stem cells one after another in different orders. They will grow and analyze the edited cells to see which mutation sequences cause cells to behave like acute myeloid leukemia and become engraftable. The team will compare molecular signals, cell behavior, and how mutations cooperate to identify patterns that drive leukemogenesis. Results aim to reveal biological rules that explain why some mutation combinations are more harmful than others.

Who could benefit from this research

Good fit: Patients with acute myeloid leukemia—especially those whose leukemia carries ASXL1, SRSF2, or NRAS mutations—would be most relevant to related future studies.

Not a fit: People with other cancers, healthy volunteers, or AML patients who lack these specific mutations are unlikely to benefit directly from this project in the near term.

Why it matters

Potential benefit: If successful, this work could explain why certain mutation orders produce more aggressive AML and help guide prognosis or targeted treatment development.

How similar studies have performed: The team has previously created an engraftable AML model from human iPSCs with three driver mutations, showing the approach can work, but applying mutation order to explain clinical outcomes is still a new direction.

Where this research is happening

New York, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.