HTLV1, Adult Tcell Leukemia, and Aneuploidy

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HTLV-1, Adult T-cell Leukemia, and Aneuploidy

Kuan-Teh Jeang, NIAID, NIH
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HTLV-1 Genomic Organization
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Aneuploidy and Cancers

• 70 to 80 of all cancers are associated with
  aneuploidy (by comparison only 50 of cancers
  have p53 changes).
• One emerging view is that aneuploidy is the
  cause, as opposed to the consequence, of
  transformation.
• Virtually all ATL/HTLV cells are aneuploid.

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Human cells transfected with Tax
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• Centrosome aberrations are common in spontaneous
  malignancies.

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How about in Tax-expressing cells?
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Tax is associated with centrosomes
A)
B)
prometaphase
metaphase
Pericentrin
GFP-Tax
anaphase
early telophase
DIC
Merge
24h after transfection
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Tax induces centrosome fragmentation
Normal cells
Ran-GTP
48h after transfection
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in primary human fibroblasts too
BJ control
BJ Tax
Staining
?-tubulin
DNA
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Conclusions Both creation (centrosome) and
tolerance (checkpoint) of DNA damage are
important for transformation. HTLV-1 encodes an
oncoprotein, Tax, that accomplishes both.
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