Contributions
Abstract: PB2056
Type: Publication Only
Background
JAK2 (V617F) gene mutation is found in approximately 60% of patients with Essential Thrombocythemia (ET), while 5-10% of JAK2 (V617F) negative ET patients carry MPL gene mutations involving codon 515. Recently, mutations at the exon 9 of calreticulin (CALR) gene have been identified in approximately 50% of patients with ET, unmutated for Jak2 and MPL.
Aims
Primary aim of the current study was to analyze the prevalence of JAK2, MPL and CALR gene mutations in patients with ET; secondary aim was to evaluate the impact of gene mutations on clinical features of ET at diagnosis.
Methods
A cohort of consecutive patients with a diagnosis of ET followed between January 2013 and June 2016 were considered. JAK2 (V617F) gene mutation was detected by PCR testing; MPL and CALR mutations were analyzed by direct sequencing methods. Thrombotic risk score was calculated according to European Leukemia Net recommendations. Data were statistically analyzed.
Results
Overall, 148 patients were included: 107 (72, 30%) had JAK2 (V617F) gene mutation (JAK2+), 12 (8, 10%) carried a mutation at exon 9 of CALR gene (CALR+), 3 (2, 02%) carried a mutation at codon 515 of MPL gene, 26 (17.58%) patients were not mutated for JAK2, CALR and MPL genes (triple negative).CALR+ subjects, compared to JAK2+ patients, had a younger age at diagnosis: median 48 year (25-92) in CALR+ patients vs 72 years (18-93, respectively. Patients with MPL mutation had a median age of 82 years while triple negative subjects had a median age of 59 years (23-89). The mean score for thrombotic risk was 0 in CALR+ patients and 1 in JAK2+, MPL+ and triple negative patients. The distribution of International Prognostic Score for Essential Thrombocythemia (IPSET) categories was also statistically significantly different (p=0.003) for the three groups. The percentage of high-risk patients was 0 in CALR+ (0/12) group, 25, 60% (27/107) in JAK2+ group, and 18, 30 % (5/26) in the triple negative group. The IPSETt model also stratified patients with statistically significant difference (p=0.001) among the three groups: the percentage of high-risk patients was 16, 66 (2/12) in the CALR+ group, 82, 35 % (88/107) in the JAK2+ group, and 33, 33(9/29) in triple negative group. CALR+ patients belonged more frequently to the low /intermediate risk group than JAK2 +patients (80% versus 17, 5%, p=0.05). The incidence of thrombotic events at diagnosis of ET was 0 in the CALR+ group, 28,03% (30/107) in the JAK2+ group and 23,07% (6 /26) in the triple negative group. The median overall survival was not reached in any group.
Conclusion
CALR+ patients with ET are phenotypically distinct from JAK2 + and triple negative patients. We can speculate a potential protective role of CALR mutation given the absence of thrombosis in IPSS and IPSETt high-risk patients.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Risk factor, Clinical data
Abstract: PB2056
Type: Publication Only
Background
JAK2 (V617F) gene mutation is found in approximately 60% of patients with Essential Thrombocythemia (ET), while 5-10% of JAK2 (V617F) negative ET patients carry MPL gene mutations involving codon 515. Recently, mutations at the exon 9 of calreticulin (CALR) gene have been identified in approximately 50% of patients with ET, unmutated for Jak2 and MPL.
Aims
Primary aim of the current study was to analyze the prevalence of JAK2, MPL and CALR gene mutations in patients with ET; secondary aim was to evaluate the impact of gene mutations on clinical features of ET at diagnosis.
Methods
A cohort of consecutive patients with a diagnosis of ET followed between January 2013 and June 2016 were considered. JAK2 (V617F) gene mutation was detected by PCR testing; MPL and CALR mutations were analyzed by direct sequencing methods. Thrombotic risk score was calculated according to European Leukemia Net recommendations. Data were statistically analyzed.
Results
Overall, 148 patients were included: 107 (72, 30%) had JAK2 (V617F) gene mutation (JAK2+), 12 (8, 10%) carried a mutation at exon 9 of CALR gene (CALR+), 3 (2, 02%) carried a mutation at codon 515 of MPL gene, 26 (17.58%) patients were not mutated for JAK2, CALR and MPL genes (triple negative).CALR+ subjects, compared to JAK2+ patients, had a younger age at diagnosis: median 48 year (25-92) in CALR+ patients vs 72 years (18-93, respectively. Patients with MPL mutation had a median age of 82 years while triple negative subjects had a median age of 59 years (23-89). The mean score for thrombotic risk was 0 in CALR+ patients and 1 in JAK2+, MPL+ and triple negative patients. The distribution of International Prognostic Score for Essential Thrombocythemia (IPSET) categories was also statistically significantly different (p=0.003) for the three groups. The percentage of high-risk patients was 0 in CALR+ (0/12) group, 25, 60% (27/107) in JAK2+ group, and 18, 30 % (5/26) in the triple negative group. The IPSETt model also stratified patients with statistically significant difference (p=0.001) among the three groups: the percentage of high-risk patients was 16, 66 (2/12) in the CALR+ group, 82, 35 % (88/107) in the JAK2+ group, and 33, 33(9/29) in triple negative group. CALR+ patients belonged more frequently to the low /intermediate risk group than JAK2 +patients (80% versus 17, 5%, p=0.05). The incidence of thrombotic events at diagnosis of ET was 0 in the CALR+ group, 28,03% (30/107) in the JAK2+ group and 23,07% (6 /26) in the triple negative group. The median overall survival was not reached in any group.
Conclusion
CALR+ patients with ET are phenotypically distinct from JAK2 + and triple negative patients. We can speculate a potential protective role of CALR mutation given the absence of thrombosis in IPSS and IPSETt high-risk patients.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Risk factor, Clinical data