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Myb & Leukemia

Myb & Leukemia. Michell Chang March 25, 2003. 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 myb proteins

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Myb & Leukemia

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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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