Contributions
Abstract: EP1084
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Clinical
Background
Myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis that can affect atypical sites, such as splanchnic vein thrombosis (SVT). In some cases, SVT precedes the MPN diagnosis whereas in other cases it occurs sometime after. MPN patients presenting with SVT are usually younger, have less abnormal blood counts and lower JAK2V617F allele burden than other MPN patients. However, it is unknown whether clinical and genetic characteristics are different according to SVT chronology.
Aims
The main aim of the present study is to describe the clinical and genomic profile of MPN associated with SVT occurring before, concurrent or after the diagnosis of MPN.
Methods
Ninety-two patients with MPN and SVT were selected. Cases were divided in three categories: Group 1 included patients diagnosed of SVT before MPN; group 2, cases with concurrent diagnoses of MPN and SVT; and group 3, patients with SVT being diagnosed after MPN. Next Generation Sequencing was performed and patients were classified according to the genomic classification proposed by Grinfeld.
Results
In 15 cases (16%) SVT was diagnosed before MPN, in 56 patients (61%) SVT and MPN were concurrently diagnosed and in 21 cases (23%) SVT was found after the diagnosis of MPN. Fifty-two patients (56.5%) were women. The median age was 51, 42 and 43 years in groups 1, 2, and 3, respectively.
Regarding their MPN, 52 cases (57%) fulfilled diagnostic criteria for polycythemia vera (PV), 23 cases (25%) for essential thrombocythemia and 2 (2%) for primary myelofibrosis. Thirteen cases (14%) were classified as MPN, unclassifiable (MPN-U). Group 1 was enriched in MPN-U cases (33% of group 1 cases vs 11.5% and 9.5% in groups 2 and 3, p=0.02), while group 2 was enriched with PV (69% of cases vs 47% and 43% in groups 1 and 3, p=0.02).
In comparison with group 2 and 3, group 1 patients had lower hematocrit value (median 41% vs 46% and 49%, p=0.02) and lower leukocyte count (5.8x109/L vs 9.9x109/L and 10.9 x109/L, p=0.02) whereas patients from group 3 showed higher platelet counts (630x109/L vs 339 x109/L and 410 x109/L in groups 1 and 2, respectively, p=0.02).
JAK2 gene was mutated in 85 patients: V617F mutation in 81 cases (88%), exon 12 mutation in 3 cases and non-canonical mutation in 1 case. JAK2V617F allele burden was higher in group 3 (43% vs 21% and 28% in groups 1 and 2, respectively, p=0.001). Genomic classification showed MPN with TP53 disruption/aneuploidy, MPN with chromatin/spliceosome mutation, MPN with CALR mutation, MPN with homozygous JAK2 and MPN with heterozygous JAK2 mutation in 5%, 17%, 3%, 10%, and 61% of cases, respectively. Analysis according to SVT chronology showed that groups 1 and 2 were enriched in MPN with heterozygous JAK2 mutation (60% and 77% of cases, respectively, vs 37% in group 3, p=0.01). MPN with TP53 disruption/aneuploidy was observed in 0%, 7%, and 21%, of cases in groups 1, 2 and 3, respectively. MPN with chromatin/spliceosome mutation was detected in 20%, 15% and 26% of cases in groups 1, 2, and 3 respectively. A higher number of pathogenic mutations was observed in group 3 (median: 2; range:1-6) than in group 2 (median: 1; range: 1-3) or group 1 (median 1; range: 0-4) (p=0.001).
Conclusion
Patients developing SVT after the diagnosis of MPN have higher JAK2V617F allele burden and more genomic complexity than patients with SVT diagnosed before or at MPN diagnosis. Mild or absent hematological alterations due to low genomic complexity might explain the delay in MPN diagnosis in patients with SVT preceding MPN.
Keyword(s): Mutation analysis, Myeloproliferative disorder, Thrombosis
Abstract: EP1084
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Clinical
Background
Myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis that can affect atypical sites, such as splanchnic vein thrombosis (SVT). In some cases, SVT precedes the MPN diagnosis whereas in other cases it occurs sometime after. MPN patients presenting with SVT are usually younger, have less abnormal blood counts and lower JAK2V617F allele burden than other MPN patients. However, it is unknown whether clinical and genetic characteristics are different according to SVT chronology.
Aims
The main aim of the present study is to describe the clinical and genomic profile of MPN associated with SVT occurring before, concurrent or after the diagnosis of MPN.
Methods
Ninety-two patients with MPN and SVT were selected. Cases were divided in three categories: Group 1 included patients diagnosed of SVT before MPN; group 2, cases with concurrent diagnoses of MPN and SVT; and group 3, patients with SVT being diagnosed after MPN. Next Generation Sequencing was performed and patients were classified according to the genomic classification proposed by Grinfeld.
Results
In 15 cases (16%) SVT was diagnosed before MPN, in 56 patients (61%) SVT and MPN were concurrently diagnosed and in 21 cases (23%) SVT was found after the diagnosis of MPN. Fifty-two patients (56.5%) were women. The median age was 51, 42 and 43 years in groups 1, 2, and 3, respectively.
Regarding their MPN, 52 cases (57%) fulfilled diagnostic criteria for polycythemia vera (PV), 23 cases (25%) for essential thrombocythemia and 2 (2%) for primary myelofibrosis. Thirteen cases (14%) were classified as MPN, unclassifiable (MPN-U). Group 1 was enriched in MPN-U cases (33% of group 1 cases vs 11.5% and 9.5% in groups 2 and 3, p=0.02), while group 2 was enriched with PV (69% of cases vs 47% and 43% in groups 1 and 3, p=0.02).
In comparison with group 2 and 3, group 1 patients had lower hematocrit value (median 41% vs 46% and 49%, p=0.02) and lower leukocyte count (5.8x109/L vs 9.9x109/L and 10.9 x109/L, p=0.02) whereas patients from group 3 showed higher platelet counts (630x109/L vs 339 x109/L and 410 x109/L in groups 1 and 2, respectively, p=0.02).
JAK2 gene was mutated in 85 patients: V617F mutation in 81 cases (88%), exon 12 mutation in 3 cases and non-canonical mutation in 1 case. JAK2V617F allele burden was higher in group 3 (43% vs 21% and 28% in groups 1 and 2, respectively, p=0.001). Genomic classification showed MPN with TP53 disruption/aneuploidy, MPN with chromatin/spliceosome mutation, MPN with CALR mutation, MPN with homozygous JAK2 and MPN with heterozygous JAK2 mutation in 5%, 17%, 3%, 10%, and 61% of cases, respectively. Analysis according to SVT chronology showed that groups 1 and 2 were enriched in MPN with heterozygous JAK2 mutation (60% and 77% of cases, respectively, vs 37% in group 3, p=0.01). MPN with TP53 disruption/aneuploidy was observed in 0%, 7%, and 21%, of cases in groups 1, 2 and 3, respectively. MPN with chromatin/spliceosome mutation was detected in 20%, 15% and 26% of cases in groups 1, 2, and 3 respectively. A higher number of pathogenic mutations was observed in group 3 (median: 2; range:1-6) than in group 2 (median: 1; range: 1-3) or group 1 (median 1; range: 0-4) (p=0.001).
Conclusion
Patients developing SVT after the diagnosis of MPN have higher JAK2V617F allele burden and more genomic complexity than patients with SVT diagnosed before or at MPN diagnosis. Mild or absent hematological alterations due to low genomic complexity might explain the delay in MPN diagnosis in patients with SVT preceding MPN.
Keyword(s): Mutation analysis, Myeloproliferative disorder, Thrombosis