Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin

Na Man, Xiao Jian Sun, Yurong Tan, Marta García-Cao, Fan Liu, Guoyan Cheng, Megan Hatlen, Haiming Xu, Ronit Shah, Nolan Chastain, Na Liu, Gang Huang, Yuan Zhou, Mengyao Sheng, Junhong Song, Feng-Chun Yang, Robert Benezra, Stephen D Nimer, Lan Wang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Inhibitor of DNA binding 1 (Id1) functions as an E protein inhibitor, and overexpression of Id1 is seen in acute myeloid leukemia (AML) patients. To define the effects of Id1 on leukemogenesis, we expressed MLL-AF9 in fetal liver (FL) cells or bone marrow (BM) cells isolated from wild-type, Id1-/-, p21-/-, or Id1-/- p21-/- mice, and transplanted them into syngeneic recipient mice. We found that although mice receiving MLL-AF9 - transduced FL or BM cells develop AML, loss of Id1 significantly prolonged the median survival of mice receiving FL cells but accelerated leukemogenesis in recipients of BM cells. Deletion of Cdkn1a (p21), an Id1 target gene, can rescue the effect of Id1 loss in both models, suggesting that Cdkn1a is a critical target of Id1 in leukemogenesis. It has been suggested that the FL transplant model mimics human fetal-origin (infant) MLL fusion protein (FP)-driven leukemia, whereas the BM transplantation model resembles postnatal MLL leukemia; in fact, the analysis of clinical samples from patients with MLL-FP+ leukemia showed that Id1 expression is elevated in the former and reduced in the latter type of MLL-FP+ AML. Our findings suggest that Id1 could be a potential therapeutic target for infant MLL-AF9-driven leukemia.

Original languageEnglish (US)
Pages (from-to)2322-2326
Number of pages5
JournalBlood
Volume127
Issue number19
DOIs
StatePublished - 2016

    Fingerprint

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Man, N., Sun, X. J., Tan, Y., García-Cao, M., Liu, F., Cheng, G., Hatlen, M., Xu, H., Shah, R., Chastain, N., Liu, N., Huang, G., Zhou, Y., Sheng, M., Song, J., Yang, F-C., Benezra, R., Nimer, S. D., & Wang, L. (2016). Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin. Blood, 127(19), 2322-2326. https://doi.org/10.1182/blood-2015-11-677708