Bone marrow histology in CALR mutated thrombocythemia and myelofibrosis: results from two cross sectional studies in 70 newly diagnosed JAK2/MPL wild type thrombocythemia patients

Abstract

The clinical phenotypes in 268 JAK2 V617F mutated MPN patients in the Seoul study were PV in 101, ET in 95 and MF in 78 and 56 CALR mutated MPN consisted of PV in none, ET in 40 and MF in 16 cases. CALR mutated MPN patients were younger than JAK2V 617F mutated MPN patients (mean ages 57.5 and 66 years), had lower values for values for leukocytes (8.6 vs 11.9x10 9 /L) and higher values for platelets (898 vs 643x10 9 /L respectively). Bone marrow histopathology in 268 JAK2 V617F mutated MPN patients in the Seoul study was featured by an increased erythropoiesis and megakaryopoiesis (EM) in 13.5%, an increased erythropoiesis, megakaryopoiesis and granulopoiesis (EMG) in 31.3%, a normocellular megakaryocytic (M) proliferation in 29,1%, a megakaryocytic and granulocytic (MG) proliferation with a relative reduction of erythropoiesis in post-ET and Post-PV myelofi brosis in 26.2%. The bone marrow histology in 56 cases of CALR mutated MPN show a predominantly increased megakaryopoiesis (M) in two thirds and an increased megakaryopoiesis and granulopoiesis (MG) with a decreased erythropoiesis in one third.Thirteen consecutive CALR MPN patients in the Belgian & Dutch cross sectional study presented with thrombocythemia associated with a typical PMGM bone marrow histology in 11 and myelofi brosis in 2 cases. All 11 thrombocythemia and 2 myelofi brosis CALR mutated MPN patients did not have constitutional symptoms and did not suffer from microvascular erythromelalgic disturbances, major thrombosis at platelet counts between 400 and 1000x10 9 /L. There was an occurrence of hemorrhages at platelet counts above 1000x10 9 /L in two CALR thrombocythemia cases.Bone marrow histology of CALR mutated thrombocythemia in the Seoul and Belgian/Dutch study showed loose clusters of large megakaryocytes (M) with bulky, cloud-like nuclei with a normal or a minor reduction of erythropoiesis and no increase in reticulin fi bers grade 0 or 1 (RF 0 or 1). CALR thrombocythemia patients show various degrees of increased bone marrow cellularity due to dual megakaryocytic and granulocytic (MG) proliferation featured by large megakaryocytes with roundish bulky nuclear forms and cloud-like clumsy nuclei, which are almost never seen in JAK2 V617F ET and PV. Assessment of allele burden is an independent and most important factor for all molecular variants MPN disease burden. Overt myelofi brosis with advanced post PV and or ET myelofi brosis at the bone marrow level occurred in one third (30%) of 208 evaluable JAK2 MPN patients and in 8 (14%) of 56 CALR MPN patients in the Seoul study. Research Article Bone marrow histology in CALR mutated thrombocythemia and myelofi brosis: results from two cross sectional studies in 70 newly diagnosed JAK2/MPL wild type thrombocythemia patients How to cite this article: Michiels JJ, Kim Y, Kim M, Valster F, Potters V, et al. Bone marrow histology in CALR mutated thrombocythemia and myelofi brosis: results from two cross sectional studies in 70 newly diagnosed JAK2/MPL wild type thrombocythemia patients . Int J Bone M...

Analysis of Clinical, Laboratory and Bone Marrow Features in Dominant TPO, MPL and JAK2 Germline Mutated Hereditary Essential Thrombocythemia (HET) Versus Acquired MPL515, CALR and JAK2V617F Mutated ET in Myeloproliferative Neoplasms

“…ET, prodromal PV and classical PV (Figures 6 and 7). The natural history of CALR thrombocythemia and myelofibrosis is best reflected by the degree of anemia, splenomegaly, bone marrow cellularity due to dual megakaryocytic granulocytic myeloproliferation (CALR MGM) and increase of reticulin fibrosis [19,20].…”

“…In contrast, low to decreased LAP scores has been reported recently in CALR mutated ET/PMGM cases. CALR thrombocythemia typically shows prefibrotic PMGM bone marrow histology featured by dysmorphic immature megakaryocytes with cloud-like nucle, which are never seen in JAK2 V617F mutated ET and PV and also not in acquired MPL 515 mutated thrombocythemia[18][19][20].…”