DOES THE MUTATIONAL STATUS AFFECT THE BONE MARROW MORPHOLOGICAL DATA IN PATIENTS WITH CLASSICAL PHILADELPHIA-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS?
(Abstract release date: 05/19/16)
EHA Library. Raya J. 06/09/16; 132885; E1336
Disclosure(s): No disclosures
Dr. Jose Maria Raya
Contributions
Contributions
Abstract
Abstract: E1336
Type: Eposter Presentation
Background
It is known that there may be a correlation between a genetic or molecular alteration and the presence of characteristic histomorphological changes in the bone marrow (for example, 5q- syndrome). In recent years, molecular alterations described in chronic Philadelphia-negative myeloproliferative neoplasms, mainly JAK2 V617F, calreticulin (CALR) and MPL, have gained great diagnostic and prognostic interest.
Aims
Our objective was to analyze the possible influence of the mutational status of these diseases on the histomorphological appearance of the bone marrow.
Methods
We have retrospectively studied 140 patients atended at our center between 1998 and 2013, with a diagnosis of Philadelphia-negative myeloproliferative neoplasm. The series included 44 patients with polycythemia vera (PV, male 61%, mean age 61, range 28-82), 78 with essential thrombocythemia (ET, female 62%, mean age 54, range 16-81) and 18 with primary myelofibrosis (PMF, male 61%, mean age 63, range 46-95). We determined the presence or not of the mutations for JAK2, CALR and MPL by standard methods. All patients had performed a bone marrow trephine biopsy at diagnosis, and samples were examined by two hematologists and a pathologist with proven experience on these entities. A total of 18 histopathological characteristics were analyzed: overall and differential (erythroid, myeloid and megakaryocytic) cellularity, megakaryocytes features (size, disposition in dense or loose clusters, nuclei morphology, presence of “naked” nuclei, intrasinusoidal and paratrabecular location), anormal location of immature precursors, emperipolesis, presence of lymph nodes, microvasculature density, vascular ectasia, iron stain, osteoclerosis, collagen fibers, CD34+ precursors, and intrasinusoidal hematopoiesis . Arrangement was considered when the degree of consensus included at least two observers. Statistical analysis was performed using the SPSS 17.0 version.
Results
The frequency and distribution of mutations were as follows: 1) PV: JAK2 V617F mutation in 88.4% of cases and JAK2 exon 12 mutation in 4.7%; 2) ET: JAK2 V617F mutation in 43.4% of analyzed patients, CALR mutation in 26.4% and none was carrier of MPL mutation; 3) PMF: JAK2 V617F mutation in 37.5%, CALR mutation in 31.2% and none with MPL mutation. No morphological differences were found in the bone marrow of patients diagnosed with PV or ET according to their mutational status (carriers or not of mutations in JAK2 in PV cases, and carriers or not of JAK2 or CALR mutation in patients with ET). However, some significant changes were observed in patients with PMF. In the latter group of patients, the JAK2 V617F mutation is associated with a significantly increased overall marrow cellularity when compared with CALR mutation (predominantly normocellular) (p=0.025). Meanwhile, carriers of CALR mutation, compared to those with JAK2, show significant changes in nuclear lobulation of megakaryocytes (mostly hyperlobulated versus normo- or hypolobulated in JAK2 mutated) (p=0.019). The emperipolesis phenomenon was significantly more frequent in PMF patients carrying the JAK2 V617F mutation when compared with JAK2 non-mutated (p=0.024), and a substantially higher frequency of 'naked' nuclei of megakaryocytes was observed in PMF CALR mutated cases in comparison with CALR non-mutated (p=0.035).
Conclusion
In our experience, the mutational status appears to influence the histopathological changes observed in the bone marrow of patients with primary myelofibrosis, but not in polycythemia vera or essential thrombocythemia. Further studies including a larger volume of patients are necessary to confirm these findings.
Session topic: E-poster
Keyword(s): Bone marrow biopsy, Mutation status, Myelofibrosis
Type: Eposter Presentation
Background
It is known that there may be a correlation between a genetic or molecular alteration and the presence of characteristic histomorphological changes in the bone marrow (for example, 5q- syndrome). In recent years, molecular alterations described in chronic Philadelphia-negative myeloproliferative neoplasms, mainly JAK2 V617F, calreticulin (CALR) and MPL, have gained great diagnostic and prognostic interest.
Aims
Our objective was to analyze the possible influence of the mutational status of these diseases on the histomorphological appearance of the bone marrow.
Methods
We have retrospectively studied 140 patients atended at our center between 1998 and 2013, with a diagnosis of Philadelphia-negative myeloproliferative neoplasm. The series included 44 patients with polycythemia vera (PV, male 61%, mean age 61, range 28-82), 78 with essential thrombocythemia (ET, female 62%, mean age 54, range 16-81) and 18 with primary myelofibrosis (PMF, male 61%, mean age 63, range 46-95). We determined the presence or not of the mutations for JAK2, CALR and MPL by standard methods. All patients had performed a bone marrow trephine biopsy at diagnosis, and samples were examined by two hematologists and a pathologist with proven experience on these entities. A total of 18 histopathological characteristics were analyzed: overall and differential (erythroid, myeloid and megakaryocytic) cellularity, megakaryocytes features (size, disposition in dense or loose clusters, nuclei morphology, presence of “naked” nuclei, intrasinusoidal and paratrabecular location), anormal location of immature precursors, emperipolesis, presence of lymph nodes, microvasculature density, vascular ectasia, iron stain, osteoclerosis, collagen fibers, CD34+ precursors, and intrasinusoidal hematopoiesis . Arrangement was considered when the degree of consensus included at least two observers. Statistical analysis was performed using the SPSS 17.0 version.
Results
The frequency and distribution of mutations were as follows: 1) PV: JAK2 V617F mutation in 88.4% of cases and JAK2 exon 12 mutation in 4.7%; 2) ET: JAK2 V617F mutation in 43.4% of analyzed patients, CALR mutation in 26.4% and none was carrier of MPL mutation; 3) PMF: JAK2 V617F mutation in 37.5%, CALR mutation in 31.2% and none with MPL mutation. No morphological differences were found in the bone marrow of patients diagnosed with PV or ET according to their mutational status (carriers or not of mutations in JAK2 in PV cases, and carriers or not of JAK2 or CALR mutation in patients with ET). However, some significant changes were observed in patients with PMF. In the latter group of patients, the JAK2 V617F mutation is associated with a significantly increased overall marrow cellularity when compared with CALR mutation (predominantly normocellular) (p=0.025). Meanwhile, carriers of CALR mutation, compared to those with JAK2, show significant changes in nuclear lobulation of megakaryocytes (mostly hyperlobulated versus normo- or hypolobulated in JAK2 mutated) (p=0.019). The emperipolesis phenomenon was significantly more frequent in PMF patients carrying the JAK2 V617F mutation when compared with JAK2 non-mutated (p=0.024), and a substantially higher frequency of 'naked' nuclei of megakaryocytes was observed in PMF CALR mutated cases in comparison with CALR non-mutated (p=0.035).
Conclusion
In our experience, the mutational status appears to influence the histopathological changes observed in the bone marrow of patients with primary myelofibrosis, but not in polycythemia vera or essential thrombocythemia. Further studies including a larger volume of patients are necessary to confirm these findings.
Session topic: E-poster
Keyword(s): Bone marrow biopsy, Mutation status, Myelofibrosis
Abstract: E1336
Type: Eposter Presentation
Background
It is known that there may be a correlation between a genetic or molecular alteration and the presence of characteristic histomorphological changes in the bone marrow (for example, 5q- syndrome). In recent years, molecular alterations described in chronic Philadelphia-negative myeloproliferative neoplasms, mainly JAK2 V617F, calreticulin (CALR) and MPL, have gained great diagnostic and prognostic interest.
Aims
Our objective was to analyze the possible influence of the mutational status of these diseases on the histomorphological appearance of the bone marrow.
Methods
We have retrospectively studied 140 patients atended at our center between 1998 and 2013, with a diagnosis of Philadelphia-negative myeloproliferative neoplasm. The series included 44 patients with polycythemia vera (PV, male 61%, mean age 61, range 28-82), 78 with essential thrombocythemia (ET, female 62%, mean age 54, range 16-81) and 18 with primary myelofibrosis (PMF, male 61%, mean age 63, range 46-95). We determined the presence or not of the mutations for JAK2, CALR and MPL by standard methods. All patients had performed a bone marrow trephine biopsy at diagnosis, and samples were examined by two hematologists and a pathologist with proven experience on these entities. A total of 18 histopathological characteristics were analyzed: overall and differential (erythroid, myeloid and megakaryocytic) cellularity, megakaryocytes features (size, disposition in dense or loose clusters, nuclei morphology, presence of “naked” nuclei, intrasinusoidal and paratrabecular location), anormal location of immature precursors, emperipolesis, presence of lymph nodes, microvasculature density, vascular ectasia, iron stain, osteoclerosis, collagen fibers, CD34+ precursors, and intrasinusoidal hematopoiesis . Arrangement was considered when the degree of consensus included at least two observers. Statistical analysis was performed using the SPSS 17.0 version.
Results
The frequency and distribution of mutations were as follows: 1) PV: JAK2 V617F mutation in 88.4% of cases and JAK2 exon 12 mutation in 4.7%; 2) ET: JAK2 V617F mutation in 43.4% of analyzed patients, CALR mutation in 26.4% and none was carrier of MPL mutation; 3) PMF: JAK2 V617F mutation in 37.5%, CALR mutation in 31.2% and none with MPL mutation. No morphological differences were found in the bone marrow of patients diagnosed with PV or ET according to their mutational status (carriers or not of mutations in JAK2 in PV cases, and carriers or not of JAK2 or CALR mutation in patients with ET). However, some significant changes were observed in patients with PMF. In the latter group of patients, the JAK2 V617F mutation is associated with a significantly increased overall marrow cellularity when compared with CALR mutation (predominantly normocellular) (p=0.025). Meanwhile, carriers of CALR mutation, compared to those with JAK2, show significant changes in nuclear lobulation of megakaryocytes (mostly hyperlobulated versus normo- or hypolobulated in JAK2 mutated) (p=0.019). The emperipolesis phenomenon was significantly more frequent in PMF patients carrying the JAK2 V617F mutation when compared with JAK2 non-mutated (p=0.024), and a substantially higher frequency of 'naked' nuclei of megakaryocytes was observed in PMF CALR mutated cases in comparison with CALR non-mutated (p=0.035).
Conclusion
In our experience, the mutational status appears to influence the histopathological changes observed in the bone marrow of patients with primary myelofibrosis, but not in polycythemia vera or essential thrombocythemia. Further studies including a larger volume of patients are necessary to confirm these findings.
Session topic: E-poster
Keyword(s): Bone marrow biopsy, Mutation status, Myelofibrosis
Type: Eposter Presentation
Background
It is known that there may be a correlation between a genetic or molecular alteration and the presence of characteristic histomorphological changes in the bone marrow (for example, 5q- syndrome). In recent years, molecular alterations described in chronic Philadelphia-negative myeloproliferative neoplasms, mainly JAK2 V617F, calreticulin (CALR) and MPL, have gained great diagnostic and prognostic interest.
Aims
Our objective was to analyze the possible influence of the mutational status of these diseases on the histomorphological appearance of the bone marrow.
Methods
We have retrospectively studied 140 patients atended at our center between 1998 and 2013, with a diagnosis of Philadelphia-negative myeloproliferative neoplasm. The series included 44 patients with polycythemia vera (PV, male 61%, mean age 61, range 28-82), 78 with essential thrombocythemia (ET, female 62%, mean age 54, range 16-81) and 18 with primary myelofibrosis (PMF, male 61%, mean age 63, range 46-95). We determined the presence or not of the mutations for JAK2, CALR and MPL by standard methods. All patients had performed a bone marrow trephine biopsy at diagnosis, and samples were examined by two hematologists and a pathologist with proven experience on these entities. A total of 18 histopathological characteristics were analyzed: overall and differential (erythroid, myeloid and megakaryocytic) cellularity, megakaryocytes features (size, disposition in dense or loose clusters, nuclei morphology, presence of “naked” nuclei, intrasinusoidal and paratrabecular location), anormal location of immature precursors, emperipolesis, presence of lymph nodes, microvasculature density, vascular ectasia, iron stain, osteoclerosis, collagen fibers, CD34+ precursors, and intrasinusoidal hematopoiesis . Arrangement was considered when the degree of consensus included at least two observers. Statistical analysis was performed using the SPSS 17.0 version.
Results
The frequency and distribution of mutations were as follows: 1) PV: JAK2 V617F mutation in 88.4% of cases and JAK2 exon 12 mutation in 4.7%; 2) ET: JAK2 V617F mutation in 43.4% of analyzed patients, CALR mutation in 26.4% and none was carrier of MPL mutation; 3) PMF: JAK2 V617F mutation in 37.5%, CALR mutation in 31.2% and none with MPL mutation. No morphological differences were found in the bone marrow of patients diagnosed with PV or ET according to their mutational status (carriers or not of mutations in JAK2 in PV cases, and carriers or not of JAK2 or CALR mutation in patients with ET). However, some significant changes were observed in patients with PMF. In the latter group of patients, the JAK2 V617F mutation is associated with a significantly increased overall marrow cellularity when compared with CALR mutation (predominantly normocellular) (p=0.025). Meanwhile, carriers of CALR mutation, compared to those with JAK2, show significant changes in nuclear lobulation of megakaryocytes (mostly hyperlobulated versus normo- or hypolobulated in JAK2 mutated) (p=0.019). The emperipolesis phenomenon was significantly more frequent in PMF patients carrying the JAK2 V617F mutation when compared with JAK2 non-mutated (p=0.024), and a substantially higher frequency of 'naked' nuclei of megakaryocytes was observed in PMF CALR mutated cases in comparison with CALR non-mutated (p=0.035).
Conclusion
In our experience, the mutational status appears to influence the histopathological changes observed in the bone marrow of patients with primary myelofibrosis, but not in polycythemia vera or essential thrombocythemia. Further studies including a larger volume of patients are necessary to confirm these findings.
Session topic: E-poster
Keyword(s): Bone marrow biopsy, Mutation status, Myelofibrosis
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