Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis.
Background The MPL(Ser505Asn) mutation has been reported to be a cause of hereditary thrombocythemia. Recently, we detected this mutation in a large proportion of children with familial thrombocythemia, suggesting that in Italy the incidence of MPL(Ser505Asn) mutation could be underestimated.


METHODS
We extended the search for this mutation to all patients with essential thrombocythemia who had a positive family history for thrombocytosis or essential thrombocythemia. We identified eight Italian families positive for the MPL(Ser505Asn) mutation. Clinical and hematologic data were available for members of seven families, including 21 patients with a proven mutation and 20 relatives with thrombocytosis.


RESULTS
Fifteen major thrombotic episodes, nine of which were fatal, were recorded among 41 patients. The thrombotic manifestation was stroke in four cases, myocardial infarction in seven cases, fetal loss in two cases, deep vein thrombosis of the leg in one case and Budd Chiari syndrome in one case. Almost all patients over 20 years old had splenomegaly and bone marrow fibrosis, while these were rarely observed in patients under 20 years old, suggesting that these manifestations are associated with aging. Finally, the life expectancy of family members with thrombocytosis was significantly shorter than that of members without thrombocytosis (P=0.003). Conclusions Patients with familial thrombocytosis caused by a MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy.
Teofili
Luciana
L
Department of Hematology, Catholic University, Rome, Italy.
Giona
Fiorina
F
Torti
Lorenza
L
Cenci
Tonia
T
Ricerca
Bianca Maria
BM
Rumi
Carlo
C
Nunes
Vittorio
V
Foà
Robin
R
Leone
Giuseppe
G
Martini
Maurizio
M
Larocca
Luigi Maria
LM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics*; D001216:Asparagine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000401:mortality; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D012307:Risk Factors; D012694:Serine / Q000235:genetics; D013163:Splenomegaly / Q000235:genetics* / Q000401:mortality; D013922:Thrombocytosis / Q000150:complications / Q000235:genetics* / Q000401:mortality; D013926:Thrombopoietin / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000235:genetics* / Q000401:mortality; D055815:Young Adult
D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D012694:Serine; D001216:Asparagine; D013926:Thrombopoietin