Analysis of phenotype and outcome in essential thrombocythemia with CALR or JAK2 mutations.
The JAK2 V617F mutation, the thrombopoietin receptor MPL W515K/L mutation and calreticulin (CALR) mutations are mutually exclusive in essential thrombocythemia and support a novel molecular categorization of essential thrombocythemia. CALR mutations account for approximately 30% of cases of essential thrombocythemia. In a retrospective study, we examined the frequency of MPL and CALR mutations in JAK2 V617F-negative cases of essential thrombocythemia (n=103). In addition, we compared the clinical phenotype and outcome of CALR mutant cases of essential thrombocythemia with a cohort of JAK2 V617F-positive essential thrombocythemia (n=57). CALR-positive cases represented 63.7% of double-negative cases of essential thrombocythemia, and most carried CALR type 1 or type 2 indels. However, we also identified one patient who was positive for both the JAK2 V617F and the CALR mutations. This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, leukocyte counts, hemoglobin, and hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F-positive essential thrombocythemia. Analysis of the CALR mutant group according to indel type showed that CALR type 1 deletion is strongly associated with male gender. CALR mutant patients had a better overall survival than JAK2 V617F-positive patients, in particular patients of age 60 years or younger. In conclusion, this study in a Belgian cohort of patients supports and extends the growing body of evidence that CALR mutant cases of essential thrombocythemia are phenotypically distinct from JAK2 V617F-positive cases, with regards to clinical and hematologic presentation as well as overall survival.
Center for Human Genetics, KU Leuven and University Hospitals Leuven, Belgium.
Carla
C
Al Assaf
Center for Human Genetics, KU Leuven and University Hospitals Leuven, Belgium.
Florence
F
Van Obbergh
Laboratory of Hematology, AZ -Jan, Brugge, Belgium.
Johan
J
Billiet
Center for Human Genetics, KU Leuven and University Hospitals Leuven, Belgium.
Els
E
Lierman
Department of Hematology, University Hospitals Leuven, Belgium.
Timothy
T
Devos
Department of Hematology, Mont-Godinne University Hospital, Yvoir, Belgium.
Carlos
C
Graux
Laboratory of Hematology, AZ -Jan, Brugge, Belgium.
Anne-Sophie
AS
Hervent
Laboratory of Hematology, AZ -Jan, Brugge, Belgium.
Jan
J
Emmerechts
Department of Pathology, University Hospitals Leuven, Belgium.
Thomas
T
Tousseyn
Department of Pathology, AZ Sint-Jan, Brugge, Belgium.
Pascale
P
De Paepe
Center for Human Genetics, KU Leuven and University Hospitals Leuven, Belgium.
Petros
P
Papadopoulos
Center for Human Genetics, KU Leuven and University Hospitals Leuven, Belgium.
Lucienne
L
Michaux
Center for Human Genetics, KU Leuven and University Hospitals Leuven, Belgium Department of Hematology, University Hospitals Leuven, Belgium peter.vandenberghe@uzleuven.be.
Peter
P
Vandenberghe
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D037282:Calreticulin / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010976:Platelet Count; D055728:Primary Myelofibrosis / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D053628:Receptors, Thrombopoietin / Q000235:genetics; D012189:Retrospective Studies; D012737:Sex Factors; D016019:Survival Analysis; D013920:Thrombocythemia, Essential / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000473:pathology
C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2