THERAPY OF CML

  • Claxton, David (PI)
  • Kurzrock, Razelle (PI)
  • Ming-Sheng, Lee (PI)
  • Reading, Christopher (PI)
  • Emerson, Stephen (PI)
  • Liang, Jan (PI)
  • Feinberg, Andrew (PI)
  • Deisseroth, Albert (PI)
  • Siciliano, Michael (PI)
  • Kantarjian, Hagop (PI)
  • Talpaz, Moshe (PI)
  • Andreeff, Michael (PI)
  • Kornblau, Steven (PI)
  • Thall, Peter (PI)
  • Issa, Jean-Pierre (PI)
  • Estrov, Zeev (PI)
  • Arlinghaus, Ralph Bernard (PI)
  • Deininger, Michael (PI)
  • Shpall, Elizabeth (PI)
  • Champlin, Richard (PI)
  • Belmont, John (PI)
  • Reisner, Yair (PI)
  • Austin, David (PI)
  • Issa, Kean-Pierre (PI)
  • Cortés, Jorge (PI)

Project: Research project

Description

Chronic myelogenous leukemia can be cured by bone marrow transplantation if
it is delivered early in the chronic phase of this disease. Unfortunately,
only a small percentage of patients are eligible for this therapy. The
research programs outlined in this application are designed to take
advantage of several advances which permit the regrowth of normal cells and
reduce or remove the Philadelphia chromosome positive cells systemically and
in vitro: a interferon, combined biological therapy and chemotherapy, in
vitro removal of Philadelphia chromosome positive cells in Dexter long-term
marrow culture, and bone marrow transplantation. The following specific
questions will be addressed: 1) How can biological therapy, chemotherapy, in
vitro bone marrow culture and bone marrow transplantation be combined to
promote Philadelphia chromosome negative hematopoiesis in CML; 2) Are the
diploid cells selected from Philadelphia chromosome positive marrow normal
or leukemic; 3) How can we identify patients whose Philadelphia chromosome
positive cells are sensitive or resistant to biological therapy; and 4) What
are the mechanisms through which Philadelphia chromosome positive
hematopoiesis is suppressed by biological therapy and how does resistant
evolve. New cellular and molecular means of detection of minimal residual
disease will be used to evaluate the response to these therapeutic programs.
Studies of the molecular basis of response and resistance to biological
therapy as well as the patterns of clinical responses to the therapeutic
programs proposed will be evaluated in order to extend curative therapy to
greater numbers of CML patients.
StatusFinished
Effective start/end date12/1/896/30/16

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Dendritic Cells
Immunity
Lymphocytes
Cytogenetics
Therapeutics
Inbred NOD Mouse
SCID Mice
Autografts
Lymphocyte Activation
Hematopoietic Stem Cells
Cell Communication
Interferons
Leukemia
Cell Death
Stem Cells
Bone Marrow