Preferential nuclear accumulation of JAK2V617F in CD34+ but not in granulocytic, megakaryocytic, or erythroid cells of patients with Philadelphia-negative myeloproliferative neoplasia.
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.
Rinaldi
Ciro R
CR
Hematology Division, Department of Biochemistry and Medical Biotechnology, University Federico II, Naples, Italy. Ciro.Rinaldi@ulh.nhs.uk
Rinaldi
Paola
P
Alagia
Adele
A
Gemei
Marica
M
Esposito
Nicola
N
Formiggini
Fabio
F
Martinelli
Vincenzo
V
Senyuk
Vitalyi
V
Nucifora
Giuseppina
G
Pane
Fabrizio
F
D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D041905:Erythroid Cells / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010677:Philadelphia Chromosome; D010766:Phosphorylation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018952:Antigens, CD34; D012333:RNA, Messenger; C507924:JAK2 protein, human; D053614:Janus Kinase 2