THERAPY OF AML

  • Claxton, David (PI)
  • Deisseroth, Albert (PI)
  • Siciliano, Michael (PI)
  • Benedict, William (PI)
  • Reading, Christopher (PI)
  • Liang, Jan (PI)
  • Plunkett, William (PI)
  • Thall, Peter (PI)
  • Thomas, Mattie (PI)
  • Reed, John (PI)
  • Andreeff, Michael (PI)
  • Berry, Donald (PI)
  • Kornblau, Steven (PI)
  • Croce, Carlo (PI)
  • Estey, Elihu (PI)
  • Nagarajan, Lalitha (PI)
  • Deisseroth, Albert (PI)
  • Champlin, Richard E. (PI)

Project: Research project

Description

Acute myelogenous leukemia is a disease in which the accumulation of
primitive nonfunctional precursor cells results in the death of 80% of
patients due to bleeding and infection. Although allogeneic bone marrow
transplantation is curative, only 25% of AML patients are eligible for this
therapy, and only half of these survive long term. Another 10-20% of
patients are cured by combination chemotherapy. In order to develop new
directions of therapy for AML, we are proposing to use cloned growth
regulatory molecules to specifically sensitize the leukemia cells to phase
specific agents. We will also use these growth factors to characterize the
defects present in the subsets of AML which are associated with specific
chromosomal translocations. We will use this information to identify
targets for therapy in AML. The therapy will be based on growth factor
therapy, combination chemotherapy, and bone marrow transplantation. These
treatment programs will be linked to laboratory assays which will provide
short-term molecular endpoints for the evaluation of response and minimal
residual disease. We will classify patients with respect to a
proliferative response or a differentiation induction response to a
hematopoietic growth factor. We will compare in vitro with in vivo
responses. We will compare proliferative responses in vitro and in vivo to
growth factor induced changes in growth factor receptors, cytoplasmic
signal transduction molecules, growth factor synthesis, intranuclear growth
regulatory proteins (P53 and RB), early response gene expression, and
killing of leukemic cells by phase specific agents and before and after
exposure to myeloid growth factors. We will use PCR assays specific for
each of the chromosomally defined subsets of AML to define response to
therapy, response to growth factors and minimal residual disease. We will
use this information to build sequential therapeutic programs which
integrate chemotherapy with growth factors, used singly and in
combinations. In this way, we hope to be able to develop therapy which is
targeted to the molecular and biological defects in these diseases, which
is less toxic to normal tissues and provides more durable remissions in all
subsets of AML.
StatusFinished
Effective start/end date6/1/928/31/15

Funding

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

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Core Binding Factors
Genes
Transcription Factors
Leukemia
Genetically Modified Animals
Myosin Heavy Chains
Cytarabine
Hematopoiesis
Acute Myeloid Leukemia
Chromosome Aberrations
Prothrombin
Cell Cycle
Complementary DNA
Research Personnel
Cell Line
Bone Marrow