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Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
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Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies

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Anti-apoptotic pathways in bone marrow and megakaryocytes in myeloproliferative neoplasia

Suzanne M Koopmans1, Harry C Schouten, Arienne M W van Marion

  • 1Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands.

Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology
|November 28, 2013
PubMed
Abstract

Insights

Myeloproliferative neoplasia (MPN) bone marrow cellularity may increase due to higher pErk and pAkt signaling and lower Bnip3 expression. Megakaryocytes play a key role, especially in essential thrombocythemia (ET).

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Bone marrow cellularity in myeloproliferative neoplasia (MPN) is linked to proliferative activity.
  • Megakaryocytes are central to MPN bone marrow pathology.
  • The JAK2(V617F) mutation activates JAK2, pErk, and PI3K-Akt signaling pathways, influencing megakaryocyte differentiation and apoptosis.

Purpose of the Study:

  • To investigate the expression of phosphorylated Erk (pErk), Akt (pAkt), p70S6k, and Bnip3 in MPN bone marrow.
  • To assess the correlation between these markers and microvessel density (MVD) in MPN.
  • To elucidate the role of megakaryocytes in MPN pathogenesis, particularly in essential thrombocythemia (ET).

Main Methods:

  • Immunohistochemical analysis of pErk, pAkt, Bnip3, p70S6k, and MVD in bone marrow biopsy sections from 36 ET, 25 polycythemia vera, and 45 primary myelofibrosis patients.
  • Automated image analysis for quantitative assessment of marker expression.
  • Real-time PCR for JAK2(V617F) mutation analysis in blood samples.

Main Results:

  • MPN megakaryocytes exhibited significantly higher expression of pErk and pAkt compared to controls, predominantly in ET patients.
  • Bnip3 expression was elevated in MPN megakaryocytes but higher in control bone marrow.
  • p70S6k expression was increased in MPN megakaryocytes, especially in ET patients, relative to controls.

Conclusions:

  • Elevated pErk and pAkt, coupled with decreased Bnip3, may contribute to increased bone marrow cellularity in MPN.
  • Megakaryocytes demonstrate a dominant role in ET pathogenesis.
  • Increased megakaryocyte counts in MPN could be attributed to enhanced pAkt and p70S6k signaling.

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