Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3

Hideaki Nakajima, Fumi Shibata, Hidetoshi Kumagai, Kazuya Shimoda, Toshio Kitamura

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Internal tandem duplication of FLT3 tyrosine kinase (FLT3-ITD) is the most prevalent mutation found in acute myelogenous leukemia (AML), having been identified in 20% to 30% of all AML patients. We have previously shown that FLT3-ITD signals mainly through the signal transducer and activator of transcription 5 (STAT5) pathway and have suggested the possible involvement of Tyk2 in STAT5 activation by FLT3-ITD. The present study addressed the role of Tyk2 in FLT3-ITD signaling in a murine bone marrow transplantation (BMT) model. Transplantation of wild-type bone marrow cells transduced with the FLT3-ITD gene induced lethal myeloproliferative disease (MPD) in the recipient mice at a median latency of 89 days. Interestingly, some mice presented the proliferation of B- or T-lymphoid blasts in various organs, a presentation that resembled acute lymphoblastic leukemia (ALL). Mice that received Tyk2-deficient bone marrow cells transduced with FLT3-ITD developed lethal MPD with a disease latency (median, 100 days) and pathologic picture similar to those of mice that received wild-type bone marrow cells. These results indicate that (1) Tyk2 is not essential for MPD induction by FLT3-ITD and (2) FLT3-ITD by itself can induce ALL in a murine BMT model.

Original languageEnglish (US)
Pages (from-to)54-59
Number of pages6
JournalInternational Journal of Hematology
Volume84
Issue number1
DOIs
StatePublished - Jul 2006

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Bone Marrow Transplantation
STAT5 Transcription Factor
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Bone Marrow Cells
Lethal Genes
Protein-Tyrosine Kinases
Transcriptional Activation
Mutation

Keywords

  • Bone marrow transplantation
  • FLT3-ITD
  • Internal tandem duplication of FLT3
  • MPD
  • Myeloproliferative disease
  • Tyk2

ASJC Scopus subject areas

  • Hematology

Cite this

Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3. / Nakajima, Hideaki; Shibata, Fumi; Kumagai, Hidetoshi; Shimoda, Kazuya; Kitamura, Toshio.

In: International Journal of Hematology, Vol. 84, No. 1, 07.2006, p. 54-59.

Research output: Contribution to journalArticle

Nakajima, H, Shibata, F, Kumagai, H, Shimoda, K & Kitamura, T 2006, 'Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3', International Journal of Hematology, vol. 84, no. 1, pp. 54-59. https://doi.org/10.1532/IJH97.06016
Nakajima, Hideaki ; Shibata, Fumi ; Kumagai, Hidetoshi ; Shimoda, Kazuya ; Kitamura, Toshio. / Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3. In: International Journal of Hematology. 2006 ; Vol. 84, No. 1. pp. 54-59.
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