Articles signed on MÆDICA, JCM:

2016 WHO Clinical Molecular and Pathological Criteria for Classification and Staging of Myeloproliferative Neoplasms (MPN) Caused by MPN Driver Mutations in the JAK2, MPL and CALR Genes in the Context of New 2016 WHO Classification: Prognostic and Therapeutic Implications

MÆDICA - a Journal of Clinical Medicine | Vol. 11, nr. 1, 2016

Jan Jacques MICHIELS, Mihaela TEVET, Adrian TRIFA, Emilia NICULESCU-MIZIL, Anca LUPU, Ana-Maria VLADAREANU, Horia BUMBEA, Anca ILEA, Camelia DOBREA, Daniela GEORGESCU, Oana PATRINOIU, Mihaela POPESCU, Meilin MURAT, Cornel DRAGAN, Felicia MIHAI, Sabina ZURAC, Silvana ANGELESCU, Anamaria IOVA, Alina POPA, Rodica GOGULESCU and Viola POPOV

ABSTRACT

The 2016 WHO-CMP classification proposal defines a broad spectrum of JAK2 V617F mutated MPN phenotypes: normocellular ET, hypercellular ET due to increased erythropoiesis (prodromal PV), hypercellular ET with megakaryocytic-granulocytic myeloproliferation and splenomegaly (EMGM or masked PV), erythrocythemic PV, early and overt classical PV, advanced PV with MF and post-PV MF. ET heterozygous for the JAK2 V617F mutation is associated with low JAK2 mutation load and normal life expectance. PV patients are hetero-homozygous versus homozygous for the JAK2 V617F mutation in their early versus advanced stages with increasing JAK2 mutation load from less than 50% to 100% and increase of MPN disease burden during life long follow-up in terms of symptomatic splenomegaly, constitutional symptoms, bone marrow hypercellularity and secondary MF. Pretreatment bone marrow biopsy in prefibrotic MPNs is of diagnostic and prognostic importance. JAK2 exon 12 mutated MPN is a distinct benign early stage PV. CALR mutated hypercellular thrombocythemia show distinct PMGM bone marrow characteristics of clustered larged immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are not seen in JAK2 mutated ET and PV. MPL mutated normocellular thrombocythemia is featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei without features of PV in blood and bone marrow. Myeloproliferative disease burden in each of the JAK2, CALR and MPL MPNs is best reflected by the degree of anemia, splenomegaly, mutation allele burden, bone marrow cellularity and myelofibrosis.

Keywords: Myeloproliferative neoplasms; Essential thrombocythemia; Polycythemia vera; Primary megakaryocytic granulocytic myeloproliferation; Myelofibrosis; JAK2V617F mutation; MPL515 mutation; Calreticulin mutation; JAK2 wild type; Bone marrow pathology

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Secondary Acute Lymphoblastic Leukemia after Hodgkin’s Lymphoma or a Coincidental Association of Two Hematological Malignancies?

Mihaela TEVET, Cornel DRAGAN, Carmen SAGUNA, Doina BARBU and Anca Roxana LUPU

ABSTRACT

Secondary acute lymphoblastic leukaemia (sALL), defined as acute lymphoblastic leukaemia following another malignancy, irrespective of previous treatment, is a rare disease, and its biological characteristics have not been accurately described. We report the case of a 24-year old patient followed for Hodgkin’s lymphoma at our clinic, who develops and is diagnosed, less than a year after obtaining complete remission, as having pro-B acute lymphoblastic leukaemia This case has been a real diagnostic and treatment challenge, as sALL following another haematological malignancy is quite rare. Conclusion: It is necessary to better identify the prognostic factors of haematological malignancies in order to prevent the appearance of sALL.

Keywords: secondary acute leukaemia, Hodgkin’s lymphoma, immunophenotyping, 11q23 mutation, alkilating agents, prognostic factors

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Influence of the JAK2 V617F Mutation and Inherited Thrombophilia on the Thrombotic Risk among Patients with Myeloproliferative Disorders

Mihaela TEVET, Razvan IONESCU, Cornel DRAGAN and Anca Roxana LUPU

ABSTRACT

Background: A number of studies showed that the JAK2 V617F mutation increases the thrombotic risk in patients with myeloproliferative disorders (MPN) while others did not reveal this correlation, and it is unknown whether inherited thrombophilia is an additive risk factor in mutated subjects. Our aim was to clarify the contribution of JAK2 V617F to a hypercoagulable state, as well as its interaction with other thrombophilic factors in patients with thrombosis and myeloproliferative disorders.

Method: We studied 192 patients with myeloproliferative disorders, 90 with Essential thrombocytemia (ET), 42 with Polycythemia vera (PV) and 60 with Primary or idiopathic myelofibrosis (PMI). From these patients a subgroup of only 62 patients underwent laboratory screening for thrombophilia.

Results: The JAK2 V617F mutation was present in 62.8% patients with myeloproliferative disorders, 97.6% with PV, 54.5 % with ET and 53.44% patients with PMI. The mutated patients had a relative risk (RR) for thrombosis at any time of 2.94 in comparison with „wild-type” patients which was 0.93; in those patients having both the mutation and thrombophilia the RR was 3.56 (95% CI 2.41-7.34) compared to patients with neither the mutation nor thrombophilia, suggesting an additive interaction between the two risk factors.

Conclusion: In patients with myeloproliferatives neoplasias, the thrombotic risk is higher in the JAK2 V617F-mutated subgroup and it is further increased by the presence of inherited thrombophilia (especially by the presence of mutated F V Leiden and lupus anticoagulant).

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Articles signed on MÆDICA, JCM:

2016 WHO Clinical Molecular and Pathological Criteria for Classification and Staging of Myeloproliferative Neoplasms (MPN) Caused by MPN Driver Mutations in the JAK2, MPL and CALR Genes in the Context of New 2016 WHO Classification: Prognostic and Therapeutic Implications

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