• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis.

To develop murine models of leukemogenesis, a series of transgenic mice expressing BCR-ABL in different hematopoietic cell subsets was generated. Here we describe targeted expression of P210 BCR-ABL in stem and progenitor cells of murine bone marrow using the tet-off system. The transactivator protein tTA was placed under the control of the murine stem cell leukemia (SCL) gene 3' enhancer. Induction of BCR-ABL resulted in neutrophilia and leukocytosis, and the mice became moribund within 29 to 122 days. Autopsy of sick mice demonstrated splenomegaly, myeloid bone marrow hyperplasia, and extramedullary myeloid cell infiltration of multiple organs. BCR-ABL mRNA and protein were detectable in the affected organs. Fluorescence-activated cell sorter (FACS) analysis demonstrated a significant increase in mature and immature myeloid cells in bone marrow and spleen, together with increased bilineal B220+/Mac-1+ cells in the bone marrow. tTA mRNA was expressed in FACS-sorted hematopoietic stem cells expanded 26-fold after BCR-ABL induction. Thirty-one percent of the animals demonstrated a biphasic phenotype, consisting of neutrophilia and subsequent B-cell lymphoblastic disease, reminiscent of blast crisis. In summary, this mouse model recapitulates many characteristics of human chronic myeloid leukemia (CML) and may help elucidate basic leukemogenic mechanisms in CML stem cells during disease initiation and progression.

Pubmed ID: 15331442

Authors

  • Koschmieder S
  • Göttgens B
  • Zhang P
  • Iwasaki-Arai J
  • Akashi K
  • Kutok JL
  • Dayaram T
  • Geary K
  • Green AR
  • Tenen DG
  • Huettner CS

Journal

Blood

Publication Data

January 1, 2005

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK48660
  • Agency: NCI NIH HHS, Id: P30CA6516

Mesh Terms

  • Animals
  • Bone Marrow
  • Cell Transformation, Neoplastic
  • Disease Models, Animal
  • Disease Progression
  • Fusion Proteins, bcr-abl
  • Hematopoietic Stem Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukocytosis
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Myeloid Cells
  • Neoplasm Invasiveness
  • Neutrophils
  • Phenotype
  • Spleen
  • Stem Cell Transplantation
  • Survival Rate
  • Transcriptional Activation