MOLECULAR CHARACTERIZATION OF ESSENTIAL THROMBOCYTHEMIA PATIENTS EVOLVED TO POLYCYTHEMIA VERA
(Abstract release date: 05/19/16)
EHA Library. Besses C. 06/09/16; 132892; E1343
Dr. Carlos Besses
Contributions
Contributions
Abstract
Abstract: E1343
Type: Eposter Presentation
Background
JAK2V617F-mutated essential thrombocythemia (ET) and polycythemia vera (PV) represent a biological spectrum of the same JAK2V617F disease modulated by several acquired and constitutional factors. In this sense, the phenotypic transformation of ET to PV occurs in 3-10% of patients. There is scarce information comparing the clinical and molecular profile of this group of patients, at baseline and at the time of transformation.
Aims
To characterize the clinical and molecular profile of a group of 10 ET patients who evolved to post-ET PV, before and after transformation.
Methods
From a whole cohort of 262 ET patients, 10 cases that evolved to post-ET PV (3.8%) were included in the study. In all patients, PV diagnosis was established according to the demonstration of an increased red cell mass (>125%). JAK2V617F was analyzed by quantitative allele specific PCR in granulocytes at ET and post-ET PV diagnosis. To determine acquisition of 9p loss of heterozygosity (LOH), breakpoints for chromosome 9p were mapped using fluorescence microsatellite PCR. Targeted next generation sequencing (NGS) was used to detect additional non-driver somatic mutations. Clonality based on X-chromosome inactivation pattern by HUMARA and JAK2 46/1 haplotype were also analyzed. The study was approved by the local Ethics Committee and informed consent was obtained according to the Declaration of Helsinki.
Results
All 10 patients (male/female: 2/8) initially diagnosed with ET according to WHO criteria fulfilled the criteria for PV after a median of 75 months (range: 13-305). One patient started cytoreductive treatment prior to the transformation. The main clinical and hematological data at the time of ET and post-ET PV are summarized in Table 1. JAK2V617F evolutionary pattern was available in 8 patients. In all instances, a progressive increase in the JAK2V617F allele burden was documented. Mitotic recombination of 9p was observed in 4/10 patients (40%) and 3 of them corresponded to the patients with higher JAK2V617F increase. Mutations in ASXL1 (n=1), DNMT3A (n=1) and TP53 (n=1) were detected at the time of transformation. Clonal hematopoiesis could not be demonstrated in any case. The JAK2 46/1 haplotype was present in 7 out of 8 available patients (87.5%), 4 in heterozygosis and 3 in homozygosis.
*Median (range). # Available in 8 patients. M: male. F: female. ET: Essential thrombocythemia. Post-ET PV: polycythemia vera post essential thrombocythemia.
Conclusion
An increase in JAK2V617F allele burden is observed in all ET patients transforming to PV and may be accompanied by other mechanisms such as acquisition of 9p LOH or additional somatic mutations. Funding. This study was supported by grants from the Ministry of Education and Science of Spain and Instituto de Salud Carlos III FEDER (FIS PI10/018087, PI13/00557, PI13/00393, RD12/0036/0010) and SGR 2014-567.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Molecular markers, Polycythemia vera
Type: Eposter Presentation
Background
JAK2V617F-mutated essential thrombocythemia (ET) and polycythemia vera (PV) represent a biological spectrum of the same JAK2V617F disease modulated by several acquired and constitutional factors. In this sense, the phenotypic transformation of ET to PV occurs in 3-10% of patients. There is scarce information comparing the clinical and molecular profile of this group of patients, at baseline and at the time of transformation.
Aims
To characterize the clinical and molecular profile of a group of 10 ET patients who evolved to post-ET PV, before and after transformation.
Methods
From a whole cohort of 262 ET patients, 10 cases that evolved to post-ET PV (3.8%) were included in the study. In all patients, PV diagnosis was established according to the demonstration of an increased red cell mass (>125%). JAK2V617F was analyzed by quantitative allele specific PCR in granulocytes at ET and post-ET PV diagnosis. To determine acquisition of 9p loss of heterozygosity (LOH), breakpoints for chromosome 9p were mapped using fluorescence microsatellite PCR. Targeted next generation sequencing (NGS) was used to detect additional non-driver somatic mutations. Clonality based on X-chromosome inactivation pattern by HUMARA and JAK2 46/1 haplotype were also analyzed. The study was approved by the local Ethics Committee and informed consent was obtained according to the Declaration of Helsinki.
Results
All 10 patients (male/female: 2/8) initially diagnosed with ET according to WHO criteria fulfilled the criteria for PV after a median of 75 months (range: 13-305). One patient started cytoreductive treatment prior to the transformation. The main clinical and hematological data at the time of ET and post-ET PV are summarized in Table 1. JAK2V617F evolutionary pattern was available in 8 patients. In all instances, a progressive increase in the JAK2V617F allele burden was documented. Mitotic recombination of 9p was observed in 4/10 patients (40%) and 3 of them corresponded to the patients with higher JAK2V617F increase. Mutations in ASXL1 (n=1), DNMT3A (n=1) and TP53 (n=1) were detected at the time of transformation. Clonal hematopoiesis could not be demonstrated in any case. The JAK2 46/1 haplotype was present in 7 out of 8 available patients (87.5%), 4 in heterozygosis and 3 in homozygosis.
| Table 1. Main clinical and hematological features at the ET and Post-ET PV diagnosis | |||
| ET | Post-ET PV | p | |
| Age (years) | 42 (32-63) | 56 (40-75) | 0.003 |
| Hemoglobin (g/l)* | 147 (123-166) | 171 (140-192) | 0.001 |
| Hematocrit (%)* | 45.1 (38-49) | 52.7 (45.6-58.9) | < 0.001 |
| Platelet count (x109/l)* | 615 (513-1064) | 916 (533-1347) | 0.097 |
| Leukocyte count (x109/l)* | 9.86 (6-15) | 12.9 (8.7-18.2) | 0.042 |
| JAK2V617F allele burden, (%) | 30.5 (16.9-42.3)# | 47.4 (25.5-84.9) | 0.006 |
Conclusion
An increase in JAK2V617F allele burden is observed in all ET patients transforming to PV and may be accompanied by other mechanisms such as acquisition of 9p LOH or additional somatic mutations. Funding. This study was supported by grants from the Ministry of Education and Science of Spain and Instituto de Salud Carlos III FEDER (FIS PI10/018087, PI13/00557, PI13/00393, RD12/0036/0010) and SGR 2014-567.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Molecular markers, Polycythemia vera
Abstract: E1343
Type: Eposter Presentation
Background
JAK2V617F-mutated essential thrombocythemia (ET) and polycythemia vera (PV) represent a biological spectrum of the same JAK2V617F disease modulated by several acquired and constitutional factors. In this sense, the phenotypic transformation of ET to PV occurs in 3-10% of patients. There is scarce information comparing the clinical and molecular profile of this group of patients, at baseline and at the time of transformation.
Aims
To characterize the clinical and molecular profile of a group of 10 ET patients who evolved to post-ET PV, before and after transformation.
Methods
From a whole cohort of 262 ET patients, 10 cases that evolved to post-ET PV (3.8%) were included in the study. In all patients, PV diagnosis was established according to the demonstration of an increased red cell mass (>125%). JAK2V617F was analyzed by quantitative allele specific PCR in granulocytes at ET and post-ET PV diagnosis. To determine acquisition of 9p loss of heterozygosity (LOH), breakpoints for chromosome 9p were mapped using fluorescence microsatellite PCR. Targeted next generation sequencing (NGS) was used to detect additional non-driver somatic mutations. Clonality based on X-chromosome inactivation pattern by HUMARA and JAK2 46/1 haplotype were also analyzed. The study was approved by the local Ethics Committee and informed consent was obtained according to the Declaration of Helsinki.
Results
All 10 patients (male/female: 2/8) initially diagnosed with ET according to WHO criteria fulfilled the criteria for PV after a median of 75 months (range: 13-305). One patient started cytoreductive treatment prior to the transformation. The main clinical and hematological data at the time of ET and post-ET PV are summarized in Table 1. JAK2V617F evolutionary pattern was available in 8 patients. In all instances, a progressive increase in the JAK2V617F allele burden was documented. Mitotic recombination of 9p was observed in 4/10 patients (40%) and 3 of them corresponded to the patients with higher JAK2V617F increase. Mutations in ASXL1 (n=1), DNMT3A (n=1) and TP53 (n=1) were detected at the time of transformation. Clonal hematopoiesis could not be demonstrated in any case. The JAK2 46/1 haplotype was present in 7 out of 8 available patients (87.5%), 4 in heterozygosis and 3 in homozygosis.
*Median (range). # Available in 8 patients. M: male. F: female. ET: Essential thrombocythemia. Post-ET PV: polycythemia vera post essential thrombocythemia.
Conclusion
An increase in JAK2V617F allele burden is observed in all ET patients transforming to PV and may be accompanied by other mechanisms such as acquisition of 9p LOH or additional somatic mutations. Funding. This study was supported by grants from the Ministry of Education and Science of Spain and Instituto de Salud Carlos III FEDER (FIS PI10/018087, PI13/00557, PI13/00393, RD12/0036/0010) and SGR 2014-567.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Molecular markers, Polycythemia vera
Type: Eposter Presentation
Background
JAK2V617F-mutated essential thrombocythemia (ET) and polycythemia vera (PV) represent a biological spectrum of the same JAK2V617F disease modulated by several acquired and constitutional factors. In this sense, the phenotypic transformation of ET to PV occurs in 3-10% of patients. There is scarce information comparing the clinical and molecular profile of this group of patients, at baseline and at the time of transformation.
Aims
To characterize the clinical and molecular profile of a group of 10 ET patients who evolved to post-ET PV, before and after transformation.
Methods
From a whole cohort of 262 ET patients, 10 cases that evolved to post-ET PV (3.8%) were included in the study. In all patients, PV diagnosis was established according to the demonstration of an increased red cell mass (>125%). JAK2V617F was analyzed by quantitative allele specific PCR in granulocytes at ET and post-ET PV diagnosis. To determine acquisition of 9p loss of heterozygosity (LOH), breakpoints for chromosome 9p were mapped using fluorescence microsatellite PCR. Targeted next generation sequencing (NGS) was used to detect additional non-driver somatic mutations. Clonality based on X-chromosome inactivation pattern by HUMARA and JAK2 46/1 haplotype were also analyzed. The study was approved by the local Ethics Committee and informed consent was obtained according to the Declaration of Helsinki.
Results
All 10 patients (male/female: 2/8) initially diagnosed with ET according to WHO criteria fulfilled the criteria for PV after a median of 75 months (range: 13-305). One patient started cytoreductive treatment prior to the transformation. The main clinical and hematological data at the time of ET and post-ET PV are summarized in Table 1. JAK2V617F evolutionary pattern was available in 8 patients. In all instances, a progressive increase in the JAK2V617F allele burden was documented. Mitotic recombination of 9p was observed in 4/10 patients (40%) and 3 of them corresponded to the patients with higher JAK2V617F increase. Mutations in ASXL1 (n=1), DNMT3A (n=1) and TP53 (n=1) were detected at the time of transformation. Clonal hematopoiesis could not be demonstrated in any case. The JAK2 46/1 haplotype was present in 7 out of 8 available patients (87.5%), 4 in heterozygosis and 3 in homozygosis.
| Table 1. Main clinical and hematological features at the ET and Post-ET PV diagnosis | |||
| ET | Post-ET PV | p | |
| Age (years) | 42 (32-63) | 56 (40-75) | 0.003 |
| Hemoglobin (g/l)* | 147 (123-166) | 171 (140-192) | 0.001 |
| Hematocrit (%)* | 45.1 (38-49) | 52.7 (45.6-58.9) | < 0.001 |
| Platelet count (x109/l)* | 615 (513-1064) | 916 (533-1347) | 0.097 |
| Leukocyte count (x109/l)* | 9.86 (6-15) | 12.9 (8.7-18.2) | 0.042 |
| JAK2V617F allele burden, (%) | 30.5 (16.9-42.3)# | 47.4 (25.5-84.9) | 0.006 |
Conclusion
An increase in JAK2V617F allele burden is observed in all ET patients transforming to PV and may be accompanied by other mechanisms such as acquisition of 9p LOH or additional somatic mutations. Funding. This study was supported by grants from the Ministry of Education and Science of Spain and Instituto de Salud Carlos III FEDER (FIS PI10/018087, PI13/00557, PI13/00393, RD12/0036/0010) and SGR 2014-567.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Molecular markers, Polycythemia vera
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