JAK2 AND CALR MUTATION STATUS DEFINES SUBTYPES OF ESSENCIAL THROMBOCYTHEMIA WITH SUBSTANTIALLY DIFFERENT CLINICAL COURSE
(Abstract release date: 05/19/16)
EHA Library. Alpoim Vieira M. 06/09/16; 132906; E1357
Dr. Mafalda Alpoim Vieira
Contributions
Contributions
Abstract
Abstract: E1357
Type: Eposter Presentation
Background
The JAK2V617F mutation is found in about 50 to 60% of cases of essential thrombocythemia (ET) while 5% to 10% of JAK2V16F negative ET patients carry MPL mutations at codon 515. Recently, mutations at exon 9 of CALR, were identified in 50% to 70% of ET patients with nonmutated JAK2 and MPL (double-negative).
Aims
To analyze the prevalence of JAK2V617, CALR and MPL mutations in a population of patients with WHO-defined ET and their association with clinical and laboratory features.
Methods
We retrospectively analyzed a cohort of ET patients in a single center, between 2010 and 2014. The JAK2V616F mutation was detected by allele-specific polymerase chain reaction (PCR) testing. For the detection of MPL exon 10 and CALR exon 9 mutations, we applied PCR amplification and Sanger sequencing.
Results
Of the 172 patients studied, 111 (64.5%) carried JAK2V617F mutation (JAK2+), 35 (20.3%) CALR mutation (CALR+), 6 (3.5%) MPLW515K/L mutation (MPL+) and 20 (11.6%) patients had nonmutated JAK2, MPL and CALR (triple-negative). These mutations were mutually exclusive and therefore, CALR-positive cases represented 63.5% of double-negative ET cases. Within the 35 CALR+ patients, 21 (60%) carried the type 1 mutation, 10 (28.6%) the type 2 mutation and 4 (11.4%) carried other less frequent indels.Compared to JAK2+ patients, CALR+ patients had a younger age at diagnosis (<60 years) (57.1% vs. 31.5%; p=0.006) and a higher platelet count (≥900x10^9/L) (51.4% vs. 26.1%; p=0.005). On the other hand, the JAK2+ patients presented a higher hemoglobin level (≥ 15g/dL) compared to CALR+ patients (45.9% vs. 20%; p= 0.006). No differences were found between type 1 and type 2 CALR+ subgroups.The distribution according to thrombotic risk classification was statistically different (p=0.003) among the two groups: the percentage of low/intermediate risk patients was 48.6% (n=17/35) in the CALR+ group vs. 22.5% (n=25/111) in the JAK2+ group.The distribution of International Prognostic Score for Essential Thrombocythemia (IPSET) categories was also statistically different (p=0.002) among the three groups analyzed: the percentage of high risk patients was 38.7% (n=43/111) in the JAK2+ group, 20% (n=7/35) in the CALR+ group and 10% (n=2/20) in the triple-negative group.The IPSET-thrombosis model also stratified patients with significant difference (p<0.001) among the three groups: the percentage of high risk patients was 82.9% (n=92/111) in the JAK2+ group, 17.1% (n=6/35) in the CALR+ group and 5% (n=1/20) in the triple-negative group. When comparing the two groups, CALR+ patients belonged more frequently to the low-risk group than those with JAK2+ (48.5% vs. 5.4%; p<0.001).The incidence of thrombotic events was 25% (n=43/172) and most occurred prior to the diagnosis of ET (74.4%; n=32/43). The group of triple-negative patients had the lower incidence of thrombotic events (5%) vs. the CALR+ group (17.1%) and vs. the JAK2+ group with the highest incidence of thrombotic events (32.4%) (p=0.015).Transformation to post-ET myelofibrosis occurred in 7 patients (3 CALR+, 2 triple-negative, 1 MPL+ and 1 JAK2+; p=0.093). The median overall survival (OS) was not reached in any group and no differences were identified in OS by univariate analysis according to mutational status (CALR+ vs. JAK2+ vs. MPL+ vs. triple-negative; p=0.3).
Conclusion
Our study confirms that CALR-mutated ET is phenotypically and biological distinct from JAK2-mutated ET with regard to clinical presentation and thrombotic risk.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Mutation status
Type: Eposter Presentation
Background
The JAK2V617F mutation is found in about 50 to 60% of cases of essential thrombocythemia (ET) while 5% to 10% of JAK2V16F negative ET patients carry MPL mutations at codon 515. Recently, mutations at exon 9 of CALR, were identified in 50% to 70% of ET patients with nonmutated JAK2 and MPL (double-negative).
Aims
To analyze the prevalence of JAK2V617, CALR and MPL mutations in a population of patients with WHO-defined ET and their association with clinical and laboratory features.
Methods
We retrospectively analyzed a cohort of ET patients in a single center, between 2010 and 2014. The JAK2V616F mutation was detected by allele-specific polymerase chain reaction (PCR) testing. For the detection of MPL exon 10 and CALR exon 9 mutations, we applied PCR amplification and Sanger sequencing.
Results
Of the 172 patients studied, 111 (64.5%) carried JAK2V617F mutation (JAK2+), 35 (20.3%) CALR mutation (CALR+), 6 (3.5%) MPLW515K/L mutation (MPL+) and 20 (11.6%) patients had nonmutated JAK2, MPL and CALR (triple-negative). These mutations were mutually exclusive and therefore, CALR-positive cases represented 63.5% of double-negative ET cases. Within the 35 CALR+ patients, 21 (60%) carried the type 1 mutation, 10 (28.6%) the type 2 mutation and 4 (11.4%) carried other less frequent indels.Compared to JAK2+ patients, CALR+ patients had a younger age at diagnosis (<60 years) (57.1% vs. 31.5%; p=0.006) and a higher platelet count (≥900x10^9/L) (51.4% vs. 26.1%; p=0.005). On the other hand, the JAK2+ patients presented a higher hemoglobin level (≥ 15g/dL) compared to CALR+ patients (45.9% vs. 20%; p= 0.006). No differences were found between type 1 and type 2 CALR+ subgroups.The distribution according to thrombotic risk classification was statistically different (p=0.003) among the two groups: the percentage of low/intermediate risk patients was 48.6% (n=17/35) in the CALR+ group vs. 22.5% (n=25/111) in the JAK2+ group.The distribution of International Prognostic Score for Essential Thrombocythemia (IPSET) categories was also statistically different (p=0.002) among the three groups analyzed: the percentage of high risk patients was 38.7% (n=43/111) in the JAK2+ group, 20% (n=7/35) in the CALR+ group and 10% (n=2/20) in the triple-negative group.The IPSET-thrombosis model also stratified patients with significant difference (p<0.001) among the three groups: the percentage of high risk patients was 82.9% (n=92/111) in the JAK2+ group, 17.1% (n=6/35) in the CALR+ group and 5% (n=1/20) in the triple-negative group. When comparing the two groups, CALR+ patients belonged more frequently to the low-risk group than those with JAK2+ (48.5% vs. 5.4%; p<0.001).The incidence of thrombotic events was 25% (n=43/172) and most occurred prior to the diagnosis of ET (74.4%; n=32/43). The group of triple-negative patients had the lower incidence of thrombotic events (5%) vs. the CALR+ group (17.1%) and vs. the JAK2+ group with the highest incidence of thrombotic events (32.4%) (p=0.015).Transformation to post-ET myelofibrosis occurred in 7 patients (3 CALR+, 2 triple-negative, 1 MPL+ and 1 JAK2+; p=0.093). The median overall survival (OS) was not reached in any group and no differences were identified in OS by univariate analysis according to mutational status (CALR+ vs. JAK2+ vs. MPL+ vs. triple-negative; p=0.3).
Conclusion
Our study confirms that CALR-mutated ET is phenotypically and biological distinct from JAK2-mutated ET with regard to clinical presentation and thrombotic risk.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Mutation status
Abstract: E1357
Type: Eposter Presentation
Background
The JAK2V617F mutation is found in about 50 to 60% of cases of essential thrombocythemia (ET) while 5% to 10% of JAK2V16F negative ET patients carry MPL mutations at codon 515. Recently, mutations at exon 9 of CALR, were identified in 50% to 70% of ET patients with nonmutated JAK2 and MPL (double-negative).
Aims
To analyze the prevalence of JAK2V617, CALR and MPL mutations in a population of patients with WHO-defined ET and their association with clinical and laboratory features.
Methods
We retrospectively analyzed a cohort of ET patients in a single center, between 2010 and 2014. The JAK2V616F mutation was detected by allele-specific polymerase chain reaction (PCR) testing. For the detection of MPL exon 10 and CALR exon 9 mutations, we applied PCR amplification and Sanger sequencing.
Results
Of the 172 patients studied, 111 (64.5%) carried JAK2V617F mutation (JAK2+), 35 (20.3%) CALR mutation (CALR+), 6 (3.5%) MPLW515K/L mutation (MPL+) and 20 (11.6%) patients had nonmutated JAK2, MPL and CALR (triple-negative). These mutations were mutually exclusive and therefore, CALR-positive cases represented 63.5% of double-negative ET cases. Within the 35 CALR+ patients, 21 (60%) carried the type 1 mutation, 10 (28.6%) the type 2 mutation and 4 (11.4%) carried other less frequent indels.Compared to JAK2+ patients, CALR+ patients had a younger age at diagnosis (<60 years) (57.1% vs. 31.5%; p=0.006) and a higher platelet count (≥900x10^9/L) (51.4% vs. 26.1%; p=0.005). On the other hand, the JAK2+ patients presented a higher hemoglobin level (≥ 15g/dL) compared to CALR+ patients (45.9% vs. 20%; p= 0.006). No differences were found between type 1 and type 2 CALR+ subgroups.The distribution according to thrombotic risk classification was statistically different (p=0.003) among the two groups: the percentage of low/intermediate risk patients was 48.6% (n=17/35) in the CALR+ group vs. 22.5% (n=25/111) in the JAK2+ group.The distribution of International Prognostic Score for Essential Thrombocythemia (IPSET) categories was also statistically different (p=0.002) among the three groups analyzed: the percentage of high risk patients was 38.7% (n=43/111) in the JAK2+ group, 20% (n=7/35) in the CALR+ group and 10% (n=2/20) in the triple-negative group.The IPSET-thrombosis model also stratified patients with significant difference (p<0.001) among the three groups: the percentage of high risk patients was 82.9% (n=92/111) in the JAK2+ group, 17.1% (n=6/35) in the CALR+ group and 5% (n=1/20) in the triple-negative group. When comparing the two groups, CALR+ patients belonged more frequently to the low-risk group than those with JAK2+ (48.5% vs. 5.4%; p<0.001).The incidence of thrombotic events was 25% (n=43/172) and most occurred prior to the diagnosis of ET (74.4%; n=32/43). The group of triple-negative patients had the lower incidence of thrombotic events (5%) vs. the CALR+ group (17.1%) and vs. the JAK2+ group with the highest incidence of thrombotic events (32.4%) (p=0.015).Transformation to post-ET myelofibrosis occurred in 7 patients (3 CALR+, 2 triple-negative, 1 MPL+ and 1 JAK2+; p=0.093). The median overall survival (OS) was not reached in any group and no differences were identified in OS by univariate analysis according to mutational status (CALR+ vs. JAK2+ vs. MPL+ vs. triple-negative; p=0.3).
Conclusion
Our study confirms that CALR-mutated ET is phenotypically and biological distinct from JAK2-mutated ET with regard to clinical presentation and thrombotic risk.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Mutation status
Type: Eposter Presentation
Background
The JAK2V617F mutation is found in about 50 to 60% of cases of essential thrombocythemia (ET) while 5% to 10% of JAK2V16F negative ET patients carry MPL mutations at codon 515. Recently, mutations at exon 9 of CALR, were identified in 50% to 70% of ET patients with nonmutated JAK2 and MPL (double-negative).
Aims
To analyze the prevalence of JAK2V617, CALR and MPL mutations in a population of patients with WHO-defined ET and their association with clinical and laboratory features.
Methods
We retrospectively analyzed a cohort of ET patients in a single center, between 2010 and 2014. The JAK2V616F mutation was detected by allele-specific polymerase chain reaction (PCR) testing. For the detection of MPL exon 10 and CALR exon 9 mutations, we applied PCR amplification and Sanger sequencing.
Results
Of the 172 patients studied, 111 (64.5%) carried JAK2V617F mutation (JAK2+), 35 (20.3%) CALR mutation (CALR+), 6 (3.5%) MPLW515K/L mutation (MPL+) and 20 (11.6%) patients had nonmutated JAK2, MPL and CALR (triple-negative). These mutations were mutually exclusive and therefore, CALR-positive cases represented 63.5% of double-negative ET cases. Within the 35 CALR+ patients, 21 (60%) carried the type 1 mutation, 10 (28.6%) the type 2 mutation and 4 (11.4%) carried other less frequent indels.Compared to JAK2+ patients, CALR+ patients had a younger age at diagnosis (<60 years) (57.1% vs. 31.5%; p=0.006) and a higher platelet count (≥900x10^9/L) (51.4% vs. 26.1%; p=0.005). On the other hand, the JAK2+ patients presented a higher hemoglobin level (≥ 15g/dL) compared to CALR+ patients (45.9% vs. 20%; p= 0.006). No differences were found between type 1 and type 2 CALR+ subgroups.The distribution according to thrombotic risk classification was statistically different (p=0.003) among the two groups: the percentage of low/intermediate risk patients was 48.6% (n=17/35) in the CALR+ group vs. 22.5% (n=25/111) in the JAK2+ group.The distribution of International Prognostic Score for Essential Thrombocythemia (IPSET) categories was also statistically different (p=0.002) among the three groups analyzed: the percentage of high risk patients was 38.7% (n=43/111) in the JAK2+ group, 20% (n=7/35) in the CALR+ group and 10% (n=2/20) in the triple-negative group.The IPSET-thrombosis model also stratified patients with significant difference (p<0.001) among the three groups: the percentage of high risk patients was 82.9% (n=92/111) in the JAK2+ group, 17.1% (n=6/35) in the CALR+ group and 5% (n=1/20) in the triple-negative group. When comparing the two groups, CALR+ patients belonged more frequently to the low-risk group than those with JAK2+ (48.5% vs. 5.4%; p<0.001).The incidence of thrombotic events was 25% (n=43/172) and most occurred prior to the diagnosis of ET (74.4%; n=32/43). The group of triple-negative patients had the lower incidence of thrombotic events (5%) vs. the CALR+ group (17.1%) and vs. the JAK2+ group with the highest incidence of thrombotic events (32.4%) (p=0.015).Transformation to post-ET myelofibrosis occurred in 7 patients (3 CALR+, 2 triple-negative, 1 MPL+ and 1 JAK2+; p=0.093). The median overall survival (OS) was not reached in any group and no differences were identified in OS by univariate analysis according to mutational status (CALR+ vs. JAK2+ vs. MPL+ vs. triple-negative; p=0.3).
Conclusion
Our study confirms that CALR-mutated ET is phenotypically and biological distinct from JAK2-mutated ET with regard to clinical presentation and thrombotic risk.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Mutation status
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