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JAK2, CALR AND MPL MUTATIONS: CORRELATION WITH PHENOTIPE DISEASE AND HISTOPATHOLOGICAL FEATURES OF BONE BIOPSY
Author(s):
Heidy Johana Campo Palacio
,
Heidy Johana Campo Palacio
Affiliations:
Haematology,JEREZ DE LA FRONTERA HOSPITAL,JEREZ DE LA FRONTERA,Spain
María José Ramírez Sánchez
,
María José Ramírez Sánchez
Affiliations:
Haematology,JEREZ DE LA FRONTERA HOSPITAL,JEREZ DE LA FRONTERA,Spain
Antonio Millan Rodríguez Fernández
,
Antonio Millan Rodríguez Fernández
Affiliations:
Pathology,JEREZ DE LA FRONTERA HOSPITAL,JEREZ DE LA FRONTERA,Spain
Lourdes Hermosín Ramos
,
Lourdes Hermosín Ramos
Affiliations:
Haematology,JEREZ DE LA FRONTERA HOSPITAL,JEREZ DE LA FRONTERA,Spain
Beatriz Bellosillo Paricio
,
Beatriz Bellosillo Paricio
Affiliations:
Pathology,Hospital del Mar,Barcelona,Spain
Estrella Carrillo Cruz
Estrella Carrillo Cruz
Affiliations:
Haematology,Hospital Virgen del Rocío,Sevilla,Spain
(Abstract release date: 05/18/17) EHA Library. H. 05/18/17; 182768; PB2054
Dr. Heidy
Dr. Heidy
Contributions
PDF Abstract
Abstract

Abstract: PB2054

Type: Publication Only

Background

Drivers mutations JAK2, CALR and MPL are mutually exclusive in Essentials thrombocytemia (ET) and these are included in the diagnostic criteria of mieloproliferative neoplasms (MPNs). Consistent with know literature, the molecular characterisation have implications in the phenotipe disease and it might be interesting to study if these are associated with the histopathological characteristics of bone marrow biopsy

Aims
The purpose of this work is analyse the correlations between clinical-biological and histological characteristics of bone marrow biopsy and the mutational status (JAK2, CALR, MPL).

Methods
The study included 76 patients with ET diagnosed according to WHO criteria at the Haemathology Departament from Hospital de Jerez from January 2005 to December 2015. We examined the prevalence, and clinical and laboratory correlations of JAK2/CALR/MPL mutations. To evaluated the histology, one pathologist with expertise in haematopathology review the bone marrow biopsies corresponding to 44 patients with ET. We incluyed only bone marrow biopsies of at least 10 mm in length and/or minimun 8 inter-trabecular areas. The pathologist only had access to age and gender data. Mutations JAK, CALR and MPL were analysed by PCR real time and sanger sequencing.

Results

There where 55 (72%) patients JAK2, 12 (15.5%) patients CALR, one patient MPL and 9 (11.8%) patients triple-negative (TN). The main clinical and laboratory features of the patients are show in Table 1. As can be seen, a 75% of patients belonged a high risk group, 18 (23%) patients presented thrombotic events before diagnosis and only 4 (5.3%) during the evolution.
Clinical and molecular characteristics of patients as age, sex, hemoglobin level and stratification of risk were statistically significant. (Table 1). Thromboembolics events seemed to be more frequent in patients with JAK2 mutation, although statistical significance was not achieved.
The correlation between histopathological characteristics and mutational status are shown in Table 2. We observed differences between the presence of laxes groups of megacaryocytes according with the mutational status and there were more frecuently in patients with CALR mutation ( p= 0.01)
With a median of follow up of 4 years (ranger 0.3-11 años) a total of 6 patients had died. Two patients evolved to overt, one of them to acute leukaemia and the other one to myelofibrosis at 66 and 44 months from ET diagnosis respectively

Conclusion

In our study we can confirm that there are differences between clinical and laboratory finding according with mutational status, as shown in previus studies. The most consistent finding of this study was the presence of laxes groups of megacaryocytes significantly higher in those with CALR mutations.
The major limitations of this study include a small number of patients and biopsies, available to analysed, this might be the mayor causes for the lack of the data demostrating clinical and histologycal relevance. But our results should not be underestimated because, to our knowledge, this is the second study thas has investigated this relation.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Abstract: PB2054

Type: Publication Only

Background

Drivers mutations JAK2, CALR and MPL are mutually exclusive in Essentials thrombocytemia (ET) and these are included in the diagnostic criteria of mieloproliferative neoplasms (MPNs). Consistent with know literature, the molecular characterisation have implications in the phenotipe disease and it might be interesting to study if these are associated with the histopathological characteristics of bone marrow biopsy

Aims
The purpose of this work is analyse the correlations between clinical-biological and histological characteristics of bone marrow biopsy and the mutational status (JAK2, CALR, MPL).

Methods
The study included 76 patients with ET diagnosed according to WHO criteria at the Haemathology Departament from Hospital de Jerez from January 2005 to December 2015. We examined the prevalence, and clinical and laboratory correlations of JAK2/CALR/MPL mutations. To evaluated the histology, one pathologist with expertise in haematopathology review the bone marrow biopsies corresponding to 44 patients with ET. We incluyed only bone marrow biopsies of at least 10 mm in length and/or minimun 8 inter-trabecular areas. The pathologist only had access to age and gender data. Mutations JAK, CALR and MPL were analysed by PCR real time and sanger sequencing.

Results

There where 55 (72%) patients JAK2, 12 (15.5%) patients CALR, one patient MPL and 9 (11.8%) patients triple-negative (TN). The main clinical and laboratory features of the patients are show in Table 1. As can be seen, a 75% of patients belonged a high risk group, 18 (23%) patients presented thrombotic events before diagnosis and only 4 (5.3%) during the evolution.
Clinical and molecular characteristics of patients as age, sex, hemoglobin level and stratification of risk were statistically significant. (Table 1). Thromboembolics events seemed to be more frequent in patients with JAK2 mutation, although statistical significance was not achieved.
The correlation between histopathological characteristics and mutational status are shown in Table 2. We observed differences between the presence of laxes groups of megacaryocytes according with the mutational status and there were more frecuently in patients with CALR mutation ( p= 0.01)
With a median of follow up of 4 years (ranger 0.3-11 años) a total of 6 patients had died. Two patients evolved to overt, one of them to acute leukaemia and the other one to myelofibrosis at 66 and 44 months from ET diagnosis respectively

Conclusion

In our study we can confirm that there are differences between clinical and laboratory finding according with mutational status, as shown in previus studies. The most consistent finding of this study was the presence of laxes groups of megacaryocytes significantly higher in those with CALR mutations.
The major limitations of this study include a small number of patients and biopsies, available to analysed, this might be the mayor causes for the lack of the data demostrating clinical and histologycal relevance. But our results should not be underestimated because, to our knowledge, this is the second study thas has investigated this relation.

Session topic: 16. Myeloproliferative neoplasms - Clinical

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