Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome

Claudia S. Huettner, Steffen Koschmieder, Hiromi Iwasaki, Junko Iwasaki-Arai, Hanna S. Radomska, Koichi Akashi, Daniel G. Tenen

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Abstract

The BCR/ABL fusion protein is found in more than 90% of patients with chronic myeloid leukemia (CML) as well as in a subset of patients with acute B-cell leukemia. We have previously described a transgenic model for an inducible and reversible acute B-cell leukemia caused by p210 BCR/ABL. Here, we describe a new model of an inducible BCR/ABL disease by directing the expression of the oncogene to megakaryocytic progenitor cells within the murine bone marrow using the tetracycline-responsive expression system under the control of human CD34 regulatory elements. The predominant feature was the development of a chronic thrombocytosis. The condition progressed with the development of splenomegaly accompanied by lymphadenopathy in some mice. Affected animals demonstrated a dramatic increase in the number of megakaryocytes in the bone marrow and the spleen, Immunohistochemistry demonstrated that the reporter gene was expressed in hematopoietic stem cells (HSCs), common myeloid progenitor (CMP) cells, as well as in megakaryocytic/erythroid progenitor cells (MEPs). Although these mice did not display the increase in granulopoiesis commonly found in chronic myeloid leukemia (CML), the phenotype closely resembles a myeloproliferative disorder affecting the megakaryocytic lineage observed in some patients with the BCR/ABL P210 translocation.

Original languageEnglish
Pages (from-to)3363-3370
Number of pages8
JournalBlood
Volume102
Issue number9
DOIs
Publication statusPublished - Nov 1 2003
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Huettner, C. S., Koschmieder, S., Iwasaki, H., Iwasaki-Arai, J., Radomska, H. S., Akashi, K., & Tenen, D. G. (2003). Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome. Blood, 102(9), 3363-3370. https://doi.org/10.1182/blood-2003-03-0768