Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders.
We searched for JAK2 exon 12 mutations in patients with JAK2 (V617F)-negative myeloproliferative disorders. Seventeen patients with polycythemia vera (PV), including 15 sporadic cases and 2 familial cases, carried deletions or duplications of exon 12 in circulating granulocytes but not in T lymphocytes. Two of the 8 mutations detected were novel, and the most frequent ones were N542-E543del and E543-D544del. Most patients with PV carrying an exon 12 mutation had isolated erythrocytosis at clinical onset, unlike patients with JAK2 (V617F)-positive PV, most of whom had also elevations in white blood cell and/or platelet counts. Both patients with familial PV carrying an exon 12 mutation had an affected sibling with JAK2 (V617F)-positive PV. Thus, several somatic mutations of JAK2 exon 12 can be found in a myeloproliferative disorder that is mainly characterized by erythrocytosis. Moreover, a genetic predisposition to acquisition of different JAK2 mutations is inherited in families with myeloproliferative disorders.
Pietra
Daniela
D
Department of Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo and University of Pavia, Pavia, Italy.
Li
Sai
S
Brisci
Angela
A
Passamonti
Francesco
F
Rumi
Elisa
E
Theocharides
Alexandre
A
Ferrari
Maurizio
M
Gisslinger
Heinz
H
Kralovics
Robert
R
Cremonesi
Laura
L
Skoda
Radek
R
Cazzola
Mario
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree; D014633:Valine / Q000235:genetics / Q000378:metabolism
D053614:Janus Kinase 2; D014633:Valine