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

Research output: Contribution to journalArticle

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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

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B-Cell Leukemia
Myeloid Progenitor Cells
Bone
Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Tetracycline
Stem cells
Bone Marrow
Thrombocytosis
Myeloproliferative Disorders
Erythroid Precursor Cells
Animals
Megakaryocytes
Fusion reactions
Genes
Splenomegaly
Hematopoietic Stem Cells
Reporter Genes
Oncogenes
Stem Cells

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

Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome. / Huettner, Claudia S.; Koschmieder, Steffen; Iwasaki, Hiromi; Iwasaki-Arai, Junko; Radomska, Hanna S.; Akashi, Koichi; Tenen, Daniel G.

In: Blood, Vol. 102, No. 9, 01.11.2003, p. 3363-3370.

Research output: Contribution to journalArticle

Huettner, CS, Koschmieder, S, Iwasaki, H, Iwasaki-Arai, J, Radomska, HS, Akashi, K & Tenen, DG 2003, 'Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome', Blood, vol. 102, no. 9, pp. 3363-3370. https://doi.org/10.1182/blood-2003-03-0768
Huettner, Claudia S. ; Koschmieder, Steffen ; Iwasaki, Hiromi ; Iwasaki-Arai, Junko ; Radomska, Hanna S. ; Akashi, Koichi ; Tenen, Daniel G. / Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome. In: Blood. 2003 ; Vol. 102, No. 9. pp. 3363-3370.
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