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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Quantitation of the JAK2V617F mutation in microdissected bone marrow trephines: Equal mutational load in myeloid lineages and rare involvement of lymphoid cells.
Am. J. Surg. Pathol. 32, 928-935 (2008)
The JAK2V617F mutation is an essential oncogenic event in Philadelphia negative chronic myeloproliferative disorders (Ph-cMPD). It is still unclear how a unique tyrosine kinase mutation can give rise to the broad clinical and morphologic spectrum of Ph-cMPD. One possible explanation could be differences in the JAK2V617F gene dosage, or different maturation stages on which myeloid lineages are affected by the mutation. The extent of lymphoid lineage involvement in JAK2V617F-positive cMPD is still controversial. We comparatively studied the zygosity status of microdissected megakaryocytes, nonmegakaryocytic hematopoietic cells, and reactive as well as neoplastic lymphoid nodules from bone marrow trephines of 61 patients with Ph-cMPD. The presence of the mutation and mutant gene dosage were determined by allele-specific polymerase chain reaction and TaqMan analysis, respectively. The mutation was detected in 22/32 (68%) cases of essential thrombocythemia, all cases of polycythemia vera, and 4/8 (50%) idiopathic myelofibrosis. Comparison of whole bone marrow sections and the different myeloid lineages showed similar percentages of the mutated allele. Restriction to a particular lineage or major differences in allele dosage were not observed, except for 2 cases in which megakaryocytes revealed a higher frequency of the mutated allele. A heterozygous JAK2V617F mutation was detected in 3/8 "reactive" lymphoid nodule in patients with Ph-cMPD, whereas all concomitant non-Hodgkin lymphoma of B-cell type were negative. These results demonstrate that different myeloid lineages usually show similar frequencies of the JAK2V617F allele. The occasional detection of JAK2V617F in benign lymphocytes points to involvement of the lympho-myeloid stem cell.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
chronic myeproliferation disorders; JAK2v617f mutation; mutational analysis; microdissection; hematopoetic lineage involvement
ISSN (print) / ISBN
0147-5185
e-ISSN
1532-0979
Zeitschrift
American Journal of Surgical Pathology, The
Quellenangaben
Band: 32,
Heft: 6,
Seiten: 928-935
Verlag
Lippincott Williams & Wilkins
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pathology (PATH)