IMPLEMENTATION OF THE JAK2 V617F MUTATION ANALYSIS IN THE DIAGNOSIS OF SUSPECTED MYELOPROLIFERATIVE NEOPLASMS IN CAPE TOWN
(Abstract release date: 05/19/16)
EHA Library. Verburgh E. 06/09/16; 134933; PB2033
Dr. Estelle Verburgh
Contributions
Contributions
Abstract
Abstract: PB2033
Type: Publication Only
Background
The Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell malignancies characterized by overproduction of one or more myeloid lineages. The discovery of the JAK2 V617F (JAK2) mutation in 2005 was a crucial step towards unraveling the pathogenesis of the MPN and finally provided a clonal marker for the diagnosis of Polycythaemia Vera (PV), Essential Thrombocytosis (ET) and Primary Myelofibrosis (PMF). Previously diagnostic guidelines of MPN were fraught with controversy due to the absence of exactly such a defining feature. The JAK2 mutation makes it possible to definitely diagnose >95% of PV, and 50-60% of both ET and PMF cases.
Aims
We retrospectively analysed our tertiary care institution patient population in whom this test was requested since its inception in 2007. JAK2 was requested in two groups: patients presenting with thrombosis and with probable MPN. We looked at the role of the JAK2 mutation analysis in the diagnostic algorithm of MPN and in patients presenting with thrombosis.
Methods
We created a database with detailed folder review of 267 patients who had undergone the JAK2 test between 2007 and 2013 in Groote Schuur Hospital. The initial presentation of each patient was analysed for two variables, namely raised cell counts (cytoses) or thrombotic complications, or both. The diagnostic algorithm for MPN implementing the JAK2 analysis was applied to each patient. In addition to JAK2, patients with sustained erythrocytosis were investigated with serum erythropoietin (s-EPO), red cell mass (RCM) and bone marrow examination (BME).
Results
Mean age at testing were 51.2 years. Male gender predominated (n=153; 57.3%). In our population 30% (n=80) of all patients and 64.5% (n=78) of MPN patients were JAK2 positive; the other 2 JAK2 positive patients had mixed myelodysplastic-myeloproliferative syndrome. One-hundred-twenty-one patients were diagnosed with an MPN: ET patients (n=38) tested JAK2 positive in 34%; PMF (n=27) in 63% and PV (n=56) 86% positive.Of the 103 patients investigated for a sustained erythrocytosis, only 56 (54%) could be confirmed as PV. RCM and s-EPO indicated a relative erythrocytosis in 24 patients, the other 23 patients had erythrocytosis of undetermined origin.Sixty-seven patients presented with thrombotic complications: 26 with MPN diagnosis (39%) and 51 (61%) where MPN was ruled out. The diagnosis of MPN was associated only with those patients who exhibited sustained cytoses while presenting with thrombosis. MPN patients presenting with thrombosis were 0.7 times as likely to be JAK2 positive as negative, the difference was not significant.
Conclusion
The JAK2 mutation analysis was positive in the majority of our MPN population in accordance with published results but in a significant minority other methods of diagnosis remain important. The percentage JAK2 positivity in the PV population was lower than previously reported. Furthermore, almost half of patients investigated for sustained erythrocytosis did not fulfil criteria for PV. These patients with relative or undetermined erythrocytosis form a significant minority where current diagnostic and pathogenetic methods are lacking.Our analysis indicates that employing the JAK2 test to uncover an underlying MPN in patients presenting with thrombosis is unlikely to yield a positive result in the absence of sustained cytoses. Proven MPN patients presenting with thrombosis were just as likely to be JAK2 negative as positive.
Session topic: E-poster
Keyword(s): Myeloproliferative disorder, Thromboembolic events
Type: Publication Only
Background
The Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell malignancies characterized by overproduction of one or more myeloid lineages. The discovery of the JAK2 V617F (JAK2) mutation in 2005 was a crucial step towards unraveling the pathogenesis of the MPN and finally provided a clonal marker for the diagnosis of Polycythaemia Vera (PV), Essential Thrombocytosis (ET) and Primary Myelofibrosis (PMF). Previously diagnostic guidelines of MPN were fraught with controversy due to the absence of exactly such a defining feature. The JAK2 mutation makes it possible to definitely diagnose >95% of PV, and 50-60% of both ET and PMF cases.
Aims
We retrospectively analysed our tertiary care institution patient population in whom this test was requested since its inception in 2007. JAK2 was requested in two groups: patients presenting with thrombosis and with probable MPN. We looked at the role of the JAK2 mutation analysis in the diagnostic algorithm of MPN and in patients presenting with thrombosis.
Methods
We created a database with detailed folder review of 267 patients who had undergone the JAK2 test between 2007 and 2013 in Groote Schuur Hospital. The initial presentation of each patient was analysed for two variables, namely raised cell counts (cytoses) or thrombotic complications, or both. The diagnostic algorithm for MPN implementing the JAK2 analysis was applied to each patient. In addition to JAK2, patients with sustained erythrocytosis were investigated with serum erythropoietin (s-EPO), red cell mass (RCM) and bone marrow examination (BME).
Results
Mean age at testing were 51.2 years. Male gender predominated (n=153; 57.3%). In our population 30% (n=80) of all patients and 64.5% (n=78) of MPN patients were JAK2 positive; the other 2 JAK2 positive patients had mixed myelodysplastic-myeloproliferative syndrome. One-hundred-twenty-one patients were diagnosed with an MPN: ET patients (n=38) tested JAK2 positive in 34%; PMF (n=27) in 63% and PV (n=56) 86% positive.Of the 103 patients investigated for a sustained erythrocytosis, only 56 (54%) could be confirmed as PV. RCM and s-EPO indicated a relative erythrocytosis in 24 patients, the other 23 patients had erythrocytosis of undetermined origin.Sixty-seven patients presented with thrombotic complications: 26 with MPN diagnosis (39%) and 51 (61%) where MPN was ruled out. The diagnosis of MPN was associated only with those patients who exhibited sustained cytoses while presenting with thrombosis. MPN patients presenting with thrombosis were 0.7 times as likely to be JAK2 positive as negative, the difference was not significant.
Conclusion
The JAK2 mutation analysis was positive in the majority of our MPN population in accordance with published results but in a significant minority other methods of diagnosis remain important. The percentage JAK2 positivity in the PV population was lower than previously reported. Furthermore, almost half of patients investigated for sustained erythrocytosis did not fulfil criteria for PV. These patients with relative or undetermined erythrocytosis form a significant minority where current diagnostic and pathogenetic methods are lacking.Our analysis indicates that employing the JAK2 test to uncover an underlying MPN in patients presenting with thrombosis is unlikely to yield a positive result in the absence of sustained cytoses. Proven MPN patients presenting with thrombosis were just as likely to be JAK2 negative as positive.
Session topic: E-poster
Keyword(s): Myeloproliferative disorder, Thromboembolic events
Abstract: PB2033
Type: Publication Only
Background
The Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell malignancies characterized by overproduction of one or more myeloid lineages. The discovery of the JAK2 V617F (JAK2) mutation in 2005 was a crucial step towards unraveling the pathogenesis of the MPN and finally provided a clonal marker for the diagnosis of Polycythaemia Vera (PV), Essential Thrombocytosis (ET) and Primary Myelofibrosis (PMF). Previously diagnostic guidelines of MPN were fraught with controversy due to the absence of exactly such a defining feature. The JAK2 mutation makes it possible to definitely diagnose >95% of PV, and 50-60% of both ET and PMF cases.
Aims
We retrospectively analysed our tertiary care institution patient population in whom this test was requested since its inception in 2007. JAK2 was requested in two groups: patients presenting with thrombosis and with probable MPN. We looked at the role of the JAK2 mutation analysis in the diagnostic algorithm of MPN and in patients presenting with thrombosis.
Methods
We created a database with detailed folder review of 267 patients who had undergone the JAK2 test between 2007 and 2013 in Groote Schuur Hospital. The initial presentation of each patient was analysed for two variables, namely raised cell counts (cytoses) or thrombotic complications, or both. The diagnostic algorithm for MPN implementing the JAK2 analysis was applied to each patient. In addition to JAK2, patients with sustained erythrocytosis were investigated with serum erythropoietin (s-EPO), red cell mass (RCM) and bone marrow examination (BME).
Results
Mean age at testing were 51.2 years. Male gender predominated (n=153; 57.3%). In our population 30% (n=80) of all patients and 64.5% (n=78) of MPN patients were JAK2 positive; the other 2 JAK2 positive patients had mixed myelodysplastic-myeloproliferative syndrome. One-hundred-twenty-one patients were diagnosed with an MPN: ET patients (n=38) tested JAK2 positive in 34%; PMF (n=27) in 63% and PV (n=56) 86% positive.Of the 103 patients investigated for a sustained erythrocytosis, only 56 (54%) could be confirmed as PV. RCM and s-EPO indicated a relative erythrocytosis in 24 patients, the other 23 patients had erythrocytosis of undetermined origin.Sixty-seven patients presented with thrombotic complications: 26 with MPN diagnosis (39%) and 51 (61%) where MPN was ruled out. The diagnosis of MPN was associated only with those patients who exhibited sustained cytoses while presenting with thrombosis. MPN patients presenting with thrombosis were 0.7 times as likely to be JAK2 positive as negative, the difference was not significant.
Conclusion
The JAK2 mutation analysis was positive in the majority of our MPN population in accordance with published results but in a significant minority other methods of diagnosis remain important. The percentage JAK2 positivity in the PV population was lower than previously reported. Furthermore, almost half of patients investigated for sustained erythrocytosis did not fulfil criteria for PV. These patients with relative or undetermined erythrocytosis form a significant minority where current diagnostic and pathogenetic methods are lacking.Our analysis indicates that employing the JAK2 test to uncover an underlying MPN in patients presenting with thrombosis is unlikely to yield a positive result in the absence of sustained cytoses. Proven MPN patients presenting with thrombosis were just as likely to be JAK2 negative as positive.
Session topic: E-poster
Keyword(s): Myeloproliferative disorder, Thromboembolic events
Type: Publication Only
Background
The Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell malignancies characterized by overproduction of one or more myeloid lineages. The discovery of the JAK2 V617F (JAK2) mutation in 2005 was a crucial step towards unraveling the pathogenesis of the MPN and finally provided a clonal marker for the diagnosis of Polycythaemia Vera (PV), Essential Thrombocytosis (ET) and Primary Myelofibrosis (PMF). Previously diagnostic guidelines of MPN were fraught with controversy due to the absence of exactly such a defining feature. The JAK2 mutation makes it possible to definitely diagnose >95% of PV, and 50-60% of both ET and PMF cases.
Aims
We retrospectively analysed our tertiary care institution patient population in whom this test was requested since its inception in 2007. JAK2 was requested in two groups: patients presenting with thrombosis and with probable MPN. We looked at the role of the JAK2 mutation analysis in the diagnostic algorithm of MPN and in patients presenting with thrombosis.
Methods
We created a database with detailed folder review of 267 patients who had undergone the JAK2 test between 2007 and 2013 in Groote Schuur Hospital. The initial presentation of each patient was analysed for two variables, namely raised cell counts (cytoses) or thrombotic complications, or both. The diagnostic algorithm for MPN implementing the JAK2 analysis was applied to each patient. In addition to JAK2, patients with sustained erythrocytosis were investigated with serum erythropoietin (s-EPO), red cell mass (RCM) and bone marrow examination (BME).
Results
Mean age at testing were 51.2 years. Male gender predominated (n=153; 57.3%). In our population 30% (n=80) of all patients and 64.5% (n=78) of MPN patients were JAK2 positive; the other 2 JAK2 positive patients had mixed myelodysplastic-myeloproliferative syndrome. One-hundred-twenty-one patients were diagnosed with an MPN: ET patients (n=38) tested JAK2 positive in 34%; PMF (n=27) in 63% and PV (n=56) 86% positive.Of the 103 patients investigated for a sustained erythrocytosis, only 56 (54%) could be confirmed as PV. RCM and s-EPO indicated a relative erythrocytosis in 24 patients, the other 23 patients had erythrocytosis of undetermined origin.Sixty-seven patients presented with thrombotic complications: 26 with MPN diagnosis (39%) and 51 (61%) where MPN was ruled out. The diagnosis of MPN was associated only with those patients who exhibited sustained cytoses while presenting with thrombosis. MPN patients presenting with thrombosis were 0.7 times as likely to be JAK2 positive as negative, the difference was not significant.
Conclusion
The JAK2 mutation analysis was positive in the majority of our MPN population in accordance with published results but in a significant minority other methods of diagnosis remain important. The percentage JAK2 positivity in the PV population was lower than previously reported. Furthermore, almost half of patients investigated for sustained erythrocytosis did not fulfil criteria for PV. These patients with relative or undetermined erythrocytosis form a significant minority where current diagnostic and pathogenetic methods are lacking.Our analysis indicates that employing the JAK2 test to uncover an underlying MPN in patients presenting with thrombosis is unlikely to yield a positive result in the absence of sustained cytoses. Proven MPN patients presenting with thrombosis were just as likely to be JAK2 negative as positive.
Session topic: E-poster
Keyword(s): Myeloproliferative disorder, Thromboembolic events
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