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The Role of Myb Transcription Factors in Leukemia and Hematopoietic Regulation

Myb proteins, including A-myb, B-myb, and c-myb, are crucial transcription factors that regulate diverse biological processes such as spermatogenesis and cell cycle control. Myb is linked to various leukemias, including myeloblastosis and lymphocytic leukemia, primarily through the oncogene v-myb. While not definitively causative, increased expression of c-myb is observed in hematopoietic tumors. Research is ongoing to develop targeted therapies, including single-chain antibodies and ribozymes, to treat these malignancies by modulating myb activity.

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The Role of Myb Transcription Factors in Leukemia and Hematopoietic Regulation

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  1. Myb & Leukemia Michell Chang March 25, 2003

  2. What is myb? • Transcription factor with a repeating DNA-binding domain of about 50 amino acids near the n-terminus • Binds to the DNA sequence (PyAACG/TG) • Structure is similar to helix-turn-helix motif

  3. 3 myb proteins • A-myb: located on chromosome 8 • B-myb: located on chromosome 20 • c-myb: located on chromosome 6 • Exact pathway is still unknown, but pim-1 and p100 have been shown to interact with c-myb

  4. What does myb do? • A-myb: spermatogenesis • B-myb: general cell cycle regulation and possibly down-regulate c-myb • c-myb: regulation of proliferation and differentiation of immature hematopoietic cells

  5. Myb in Drosophila • Drosophila has only one myb protein • Most similar to B-myb • Null mutants had an increase in mitotic arrest with abnormal chromosome number and spindle formation

  6. c-myb in Mice • myb-null is lethal in mice • Created mice that were chimeric for Rag1 and c-myb • Found that c-myb plays a role in both macrophage and lymphoid lineages

  7. Myb & Leukemia • Myeloblastosis: type of leukemia • Avian myeloblastosis virus (AMV) caused a fatal leukemia in chickens • Traced to an oncogene: v-myb • Created by insertion of a retrovirus into a highly conserved cellular proto-oncogene (c-myb)

  8. Truncation of the c-terminus is also sufficient for c-myb to become oncogenic • Truncation of the n-terminus gives rise to a more powerful transforming ability • Truncation of both the c-terminus and n-terminus has the most powerful transforming ability

  9. Myb Related Leukemias • Lymphocytic leukemia • Myeloid leukemia • Acute T-cell leukemia

  10. Problems… • Both humans and mice show that c-myb expression is up-regulated in hematopoietic tumors • Cause? • Result?

  11. Current Thoughts About myb • Although no clear link has been shown yet that c-myb is the cause of certain types of leukemias, drugs are being created that targets it as a means of treating those leukemias. • Single chain antibodies • Oligodeoxynucleotides • Ribozymes

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