P2D, INC — Department of Health and Human Services SBIR Phase I: DESCRIPTION (provided by applicant): RUNX1 is considered a beneficial tumor suppressor in
P2D, INC — SBIR Phase I award from Department of Health and Human Services.
- Amount
- $224,629
- Agency
- Department of Health and Human Services · National Institutes of Health
- Program / Phase
- SBIR · Phase I
- Solicitation
- PA13-088
- NAICS
- —
- Place of performance
- OH
- Period
- —
Description
DESCRIPTION (provided by applicant): RUNX1 is considered a beneficial tumor suppressor in myeloid neoplasms. Inhibition of RUNX1 function has been implicated as an important mechanistic event in the development of core-binding factor-(CBF)-leukemia and MLL-fusion leukemia. Inactivating RUNX1 mutations are frequently found in patients with acute myeloid leukemia (AML). However, RUNX1 mutation is usually heterozygous, complete loss of RUNX1 in AML is rare and no somatic RUNX1 mutation have been found in AMLswith common fusion proteins, such as CBF- and MLL-fusion leukemias. These data raise the possibility that a certain (low) level of RUNX1 activity is required for survival and growth of AML. We have developed human models for AML by transducing leukemogenicfusion proteins into human cord blood CD34+ cells. MLL-AF9-expressing cord blood cells cause human leukemia when transplanted into immunodeficient mice. We recently found that these AML cells critically depend on RUNX1 activity for sustained growth a