Preferential nuclear accumulation of JAK2V617F in CD34+ but not in granulocytic, megakaryocytic, or erythroid cells of patients with Philadelphia-negative myeloproliferative neoplasia

Rinaldi, Ciro R. and Rinaldi, Paola and Alagia, Adele and Gemei, Marica and Esposito, Nicola and Formiggini, Fabio and Martinelli, Vincenzo and Senyuk, Vitalyi and Nucifora, Giuseppina and Pane, Fabrizio (2010) Preferential nuclear accumulation of JAK2V617F in CD34+ but not in granulocytic, megakaryocytic, or erythroid cells of patients with Philadelphia-negative myeloproliferative neoplasia. Blood, 116 (26). pp. 6023-6026. ISSN 0006-4971

Full content URL: http://dx.doi.org/10.1182/blood-2010-08-302265

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Abstract

Recently, Dawson et al identified a previously unrecognized nuclear role of JAK2 in the phosphorylation of histone H3 in hematopoietic cell lines. We searched nuclear JAK2 in total bone marrow (BM) cells and in 4 sorted BM cell populations (CD34(+), CD15(+), CD41(+), and CD71(+)) of 10 myeloproliferative neoplasia (MPN) patients with JAK2V617F mutation and 5 patients with wild-type JAK2 MPN. Confocal immunofluorescent images and Western blot analyses of nuclear and cytoplasmic fractions found nuclear JAK2 in CD34(+) cells of 10 of 10 JAK2-mutated patients but not in patients with wild-type JAK2. JAK2 was predominantly in the cytoplasmic fraction of differentiated granulocytic, megakaryocytic, or erythroid cells obtained from all patients. JAK2V617F up-regulates LMO2 in K562 and in JAK2V617F-positive CD34(+) cells. The selective JAK2 inhibitor AG490 normalizes the LMO2 levels in V617F-positive K562 and restores the cyto-plasmic localization of JAK2.

Additional Information:published ahead of print September 22, 2010
Keywords:jak2, MPN
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
ID Code:12412
Deposited On:24 Oct 2013 16:25

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