scholarly journals CHRONIC MYELOPROLIFERATIVE NEOPLASMS: A COLLABORATIVE APPROACH

2010 ◽  
Vol 2 (2) ◽  
pp. e2010017
Author(s):  
Lisa Pieri ◽  
Paola Guglielmelli ◽  
Alessandro Maria Vannucchi
Keyword(s):  
Acute Leukemia ◽  
Clinical Course ◽  
Myeloproliferative Neoplasms ◽  
Clinical Manifestations ◽  
Primary Myelofibrosis ◽  
The Other ◽  
Collaborative Approach ◽  
Chronic Myeloproliferative Neoplasms ◽  
Key Issues ◽  
Oriented Approach

The classic chronic myeloproliferative neoplasms (MPN) include different entities that pose significant challenges for their optimal diagnosis, treatment and overall management. Polycythemia Vera and Essential Thrombocythemia are the most common among chronic myeloproliferative neoplasms (MPNs); major causes of morbidity and mortality are represented by arterial and venous thrombosis, as well as evolution to myelofibrosis or transformation to acute leukemia. However, survival is only minimally affected. Therapy aims at reducing the rate of thrombosis without increasing the risk of hematologic transformation which could be caused by exposure to cytotoxic drugs. On the other hand, survival is significantly reduced in primary myelofibrosis, and the clinical manifestations may be disabling. In the absence of therapies with the potential of curing the disease, a careful risk-oriented approach is employed for stratifying patients to the most appropriate, currently available, therapeutic options. In this brief review, we will discuss some of the key issues that can arise along the clinical course of MPNs and require an integrated, strictly patient-oriented, approach.

scholarly journals Splenomegaly impacts prognosis in essential thrombocythemia and polycythemia vera: A single center study

2019 ◽  
Vol 11 (4) ◽  
Author(s):  
Vincenzo Accurso ◽  
Marco Santoro ◽  
Simona Raso ◽  
Angelo Davide Contrino ◽  
Paolo Casimiro ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Clinical Manifestations ◽  
Primary Myelofibrosis ◽  
Thrombotic Risk ◽  
Single Center Study ◽  
The Impact ◽  
The Relationship

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019.

scholarly journals Combination approach to diagnosis and treatment of an elderly patient with chronic Ph-negative myeloproliferative neoplasm and concomitant surgical pathology. Clinical observation

MD-Onco ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 61-65
Author(s):  
Yu. E. Ryabukhina ◽  
P. A. Zeynalova ◽  
O. I. Timofeeva ◽  
F. M. Abbasbeyli ◽  
T. V. Ponomarev ◽  
...  
Keyword(s):  
Elderly Patient ◽  
Essential Thrombocythemia ◽  
Early Stage ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Primary Myelofibrosis ◽  
Left Femur ◽  
Hematopoietic Stem ◽  
Chronic Myeloproliferative Neoplasms

Chronic myeloproliferative neoplasms (CMPN), Ph-negative, are of clonal nature, develop on the level of hematopoietic stem cell and are characterized by proliferation of one or more hematopoietic pathways. Currently, the group of Ph-negative CMPN includes essential thrombocythemia, primary myelofibrosis, polycythemia vera, myeloproliferative neoplasm unclassifiable.Identification of mutations in the Jak2 (V617F), CALR, and MPL genes extended understanding of biological features of Ph-negative CMPN and improved differential diagnosis of myeloid neoplasms. Nonetheless, clinical practice still encounters difficulties in clear separation between such disorders as primary myelofibrosis, early-stage and transformation of essential thrombocythemia into myelofibrosis with high thrombocytosis. Thrombocytosis is one of the main risk factors for thromboembolic complications, especially in elderly people.A clinical case of an elderly patient with fracture of the left femur developed in the context of Ph-negative CMPN (myelofibrosis) with high level of thrombocytosis is presented which in combination with enforced long-term immobilization and presence of additional risk created danger of thrombosis and hemorrhage during surgery and in the postoperative period.

scholarly journals Aktualitások a primer myelofibrosis ellátásában

2016 ◽  
Vol 157 (39) ◽  
pp. 1547-1556
Author(s):  
Zsófia Simon ◽  
Imelda Marton ◽  
Zita Borbényi ◽  
Árpád Illés
Keyword(s):  
Treatment Approach ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Spleen Volume ◽  
Novel Therapy ◽  
Jak2 Inhibitor ◽  
Chronic Myeloproliferative Neoplasms ◽  
Associated Symptoms ◽  
Modifying Effect ◽  
Disease Modifying

Primary myelofibrosis is one of the Philadelphia negative chronic myeloproliferative neoplasms. It is a rare disease featured by cytopenias and hepatosplenomegaly. Although the etiology of the disease is still unknown, our knowledge about its pathology and prognosis has been improving in the last few years. Furthermore, the JAK2 inhibitor ruxolitinib has become available in Hungary since 2015. Beside its high efficacy in spleen volume and in reduction of myelofibrosis-associated symptoms, this novel therapy also exerts a disease-modifying effect and, therefore, ruxolitinib may improve the life expectancy too. Treatment approach of myelofibrosis has been changed these years, which gives a reason for this summary. Orv. Hetil., 2016, 157(39), 1547–1556.

Novel, Potent and Selective JAK2 Inhibitors.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3777-3777
Author(s):  
Thomas Radimerski ◽  
Fabienne Baffert ◽  
Catherine H. Regnier ◽  
Alain De Pover ◽  
Carole Pissot ◽  
...  
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Mechanistic Model ◽  
Leukemic Cell ◽  
Primary Myelofibrosis ◽  
Myeloproliferative Disorders ◽  
Amino Acid Position ◽  
Chronic Myeloproliferative Neoplasms ◽  
Promising Target ◽  
Potent Inhibition

Abstract Abstract 3777 Poster Board III-713 The recent discovery of an acquired activating point mutation in JAK2, substituting valine at amino acid position 617 for phenylalanine, has greatly improved our understanding of the molecular mechanism underlying chronic myeloproliferative neoplasms. Strikingly, the JAK2V617F mutation is found in nearly all patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia and from primary myelofibrosis. Thus, JAK2 represents a promising target for the treatment of myeloproliferative disorders and considerable efforts are ongoing to discover and develop inhibitors of the kinase. Here, we report potent inhibition of JAK2V617F and JAK2 wild type enzymes by novel small molecule inhibitors, which act in an ATP-competitive manner. The profile of a lead compound from this class will be presented that displays more than twenty-fold selectivity towards JAK2 within the JAK family, as well as excellent selectivity in broader kinase profiling. The compound blunts constitutive STAT5 phosphorylation in JAK2V617F-bearing cells, with concomitant suppression of cell proliferation and induction of apoptosis. In vivo, the inhibitor exhibited good oral bioavailability and is efficacious in suppressing leukemic cell spreading and splenomegaly in a Ba/F3 JAK2V617F cell-driven mouse mechanistic model as well as polycythemia and extramedullary erythropoiesis in mouse and rat models. Disclosures: Radimerski: Novartis: Employment, Equity Ownership. Baffert:Novartis: Employment. Regnier:Novartis: Employment. De Pover:Novartis: Employment. Pissot:Novartis: Employment. Gerspacher:Novartis: Employment. Brueggen:Novartis: Employment. Tavares:Novartis: Employment. Blasco:Novartis: Employment. Ledieu:Novartis: Employment. Nolan:Novartis: Employment. Ruetz:Novartis: Employment. Chene:Novartis: Employment. Erdmann:Novartis: Employment. Drueckes:Novartis: Employment. Furet:Novartis: Employment. Lang:Novartis: Employment. Trappe:Novartis: Employment. Vangrevelinghe:Novartis: Employment. Wartmann:Novartis: Employment. Hofmann:Novartis: Employment.

TP53 Mutation Is Rare In Primary Myelofibrosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5241-5241
Author(s):  
Wesley O. Greaves ◽  
Shalini Verma ◽  
Tigist Bisrat ◽  
Hamed Rahimi ◽  
Abhaya Paladugu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Sanger Sequencing ◽  
Tp53 Mutation ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Melting Curve ◽  
Primary Myelofibrosis ◽  
Hrm Analysis ◽  
Exon 4

Abstract Abstract 5241 Introduction TP53 is the most frequently mutated tumor suppressor gene in human cancers and is usually associated with an aggressive disease course. TP53 mutation has been described in a variety of hematopoietic neoplasms, and has been suggested to play a role in leukemic transformation of myeloproliferative neoplasms (MPN). However, the incidence as well as the clinical and pathogenetic implications of TP53 mutation in each sub-category of MPN, including primary myelofibrosis, have not been described. In this study, we investigated the presence and potential clinical significance of TP53 mutations in a large series of primary myelofibrosis cases. Patients and Methods We retrieved archival bone marrow DNA from 51 consecutive patients diagnosed with primary myelofibrosis at The University of Texas MD Anderson Cancer Center between the years 2005 and 2007. Diagnosis was based on morphologic, immunophenotypic, cytogenetic and molecular evaluation of bone marrow in conjunction with clinical data. Only 2 patients had blast counts >10% (11 and 14%). Twenty nine of 50 (58%) patients showed JAK2 p.V617F mutation and all patients were negative for BCR-ABL1 translocation on routine clinical testing. DNA samples were assessed for sequence variation in exons 4 through 9 of TP53 by both high resolution melting curve (HRM) analysis using LightCycler® 480 System (Roche, Indiana IN) and bidirectional Sanger sequencing using 3730XL DNA Analyzer (Life technologies, Carlsbad CA). Results The mean overall survival was 5.7 years. Five patients developed acute leukemia, all of whom died of disease. By Sanger sequencing, only one (1.9%) case showed an amino acid-altering mutation in TP53: c.707A>G (TAC to TGC) in codon 236 (p.Y236C) of exon 7. In addition, 8 cases showed silent mutations/single nucleotide polymorphisms of unknown significance - c.36G>A (CCG to CCA) in exon 4 (n=3) and c.213A>G (CGA to CGG) in exon 6 (n=6). The p.R72P polymorphism in exon 4 which has been described in other hematopoietic neoplasms was present in 1 patient. All cases with a mutant sequence by Sanger sequencing also showed a variant melting curve pattern by HRM analysis. The patient with TP53 mutation died 2 years after presentation from progressive myelofibrosis without developing acute leukemia. Conclusion TP53 mutation is very rare in primary myelofibrosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Macrophage frequency in the bone marrow correlates with morphologic subtype of myeloproliferative neoplasm

2020 ◽  
Vol 100 (1) ◽  
pp. 97-104
Author(s):  
David C. A. Molitor ◽  
Peter Boor ◽  
Andreas Buness ◽  
Rebekka K. Schneider ◽  
Lino L. Teichmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Clinical Course ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Primary Myelofibrosis ◽  
Neoplastic Processes ◽  
And Control

AbstractBone marrow (BM) fibrosis in myeloproliferative neoplasms (MPNs) is associated with a poor prognosis. The development of myelofibrosis and differentiation of mesenchymal stromal cells to profibrotic myofibroblasts depends on macrophages. Here, we compared macrophage frequencies in BM biopsies of MPN patients and controls (patients with non-neoplastic processes), including primary myelofibrosis (PMF, n = 18), essential thrombocythemia (ET, n = 14), polycythemia vera (PV, n = 12), and Philadelphia chromosome–positive chronic myeloid leukemia (CML, n = 9). In PMF, CD68-positive macrophages were greatly increased compared to CML (p = 0.017) and control BM (p < 0.001). Similar findings were observed by CD163 staining (PMF vs. CML: p = 0.017; PMF vs. control: p < 0.001). Moreover, CD68-positive macrophages were increased in PV compared with ET (p = 0.009) and reactive cases (p < 0.001). PMF had higher frequencies of macrophages than PV (CD68: p < 0.001; CD163: p < 0.001) and ET (CD68: p < 0.001; CD163: p < 0.001). CD163 and CD68 were often co-expressed in macrophages with stellate morphology in Philadelphia chromosome–negative MPN, resulting in a sponge-like reticular network that may be a key regulator of unbalanced hematopoiesis in the BM space and may explain differences in cellularity and clinical course.

scholarly journals Bone marrow megakaryocytic activation predicts fibrotic evolution of Philadelphia-negative myeloproliferative neoplasms.

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Mattia Schino ◽  
Vincenzo Fiorentino ◽  
Elena Rossi ◽  
Silvia Betti ◽  
Monica Di Cecca ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloproliferative Neoplasms ◽  
Rapid Evolution ◽  
Progression Free Survival ◽  
Jak2 V617f ◽  
Primary Myelofibrosis ◽  
Serum Levels ◽  
Chronic Myeloproliferative Neoplasms ◽  
Calr Mutations ◽  
Wbc Count

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have been traditionally considered as indistinctly slowly progressing conditions; recent evidence proves that a subset of cases have a rapid evolution, so that MPNs’ prognosis needs to be personalized. We identified a new morphological parameter, defined as Megakaryocytic Activation (M-ACT) based on the coexistence of megakaryocytic emperipolesis, megakaryocytes (MK) clusters formation and evidence of arrangement of collagen fibers around the perimeter of MK. We retrospectively analyzed the bone marrow biopsy of two MPNs cohorts of patients with polycythemia (PV) (n=64) and non-PV patients [including essential thrombocythemia (ET), and early/prefibrotic primary myelofibrosis (PMF)] (n=222). M-ACT showed a significant correlation with splenomegaly, white blood cell (WBC) count, and LDH serum levels in both groups, with JAK2 V617F allele burden in PV patients, and with CALR mutations, and platelet count in non-PV patients. Progression-free survival, defined as PV-to-secondary MF progression and non-PV-to-overt PMF, was worse in both PV and early/prefibrotic PMF patients with M-ACT in comparison to those without M-ACT (P<.0001). Interestingly, M-ACT was not found in the subgroup of ET patients. In conclusion, M-ACT can be helpful in the differential diagnosis of MPNs and can represent a new morphologic parameter with a predictive value for progression of MPNs.

scholarly journals Acute Myeloid Leukemia Evolving from JAK 2-Positive Primary Myelofibrosis and Concomitant CD5-Negative Mantle Cell Lymphoma: A Case Report and Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Diana O. Treaba ◽  
Salwa Khedr ◽  
Shamlal Mangray ◽  
Cynthia Jackson ◽  
Jorge J. Castillo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cell Lymphoma ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Chronic Myeloproliferative Neoplasms ◽  
Mantle Cell ◽  
Lymphoid Aggregates ◽  
Acute Myeloid

Primary myelofibrosis (formerly known as chronic idiopathic myelofibrosis), has the lowest incidence amongst the chronic myeloproliferative neoplasms and is characterized by a rather short median survival and a risk of progression to acute myeloid leukemia (AML) noted in a small subset of the cases, usually as a terminal event. As observed with other chronic myeloproliferative neoplasms, the bone marrow biopsy may harbor small lymphoid aggregates, often assumed reactive in nature. In our paper, we present a 70-year-old Caucasian male who was diagnosed with primary myelofibrosis, and after 8 years of followup and therapy developed an AML. The small lymphoid aggregates noted in his bone marrow were neoplastic in nature and represented bone marrow involvement by a CD5-negative mantle cell lymphoma (MCL) that presented without any associated lymphadenopathy. We reviewed the English medical literature to identify a single case report of simultaneous association of AML and a MCL in the bone marrow. The unusual association presented here suggests an increase in observer awareness to apparently benign lymphoid aggregates in chronic myeloproliferative neoplasms.

Mixed phenotype acute leukemia and lineage switch from lymphoblastic leukemia to myeloid leukemia in the course of Philadelphia-negative myeloproliferative neoplasm – case reports and literature review

2020 ◽  
Vol 51 (2) ◽  
pp. 112-118 ◽  
Author(s):  
Agnieszka Ożańska ◽  
Marta Sobas ◽  
Donata Szymczak ◽  
Tomasz Wróbel
Keyword(s):  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Case Reports ◽  
Lymphoblastic Leukemia ◽  
Myeloproliferative Neoplasm ◽  
Primary Myelofibrosis ◽  
Hematopoietic Stem ◽  
Lineage Switch ◽  
Mixed Phenotype

AbstractPhiladelphia-negative myeloproliferative neoplasms (Ph-neg MPNs) are characterized by clonal hematopoiesis derived from a mutated hematopoietic stem cell. Ph-neg MPNs rarely transforms into acute leukemia, and in most cases, the transformation leads to the development of acute myeloid leukemia (AML). The incidence of mixed-phenotype leukemia (MPAL) or acute lymphoblastic leukemia (ALL) with lineage switch is much rarer. The unidentified lineage of blast cells is due to the immaturity of their undifferentiated progenitors with co-expression of myeloid and lymphoid antigens. The prognosis of secondary acute leukemia transformed from Ph-neg MPN is very unfavorable, especially in MPAL or lineage switch from ALL to AML cases. Moreover, there are no therapeutic protocols for these specific leukemia subtypes. Therefore, we believe that all cases of MPAL or lineage switch leukemia should be reported. This article presents the case of a patient with JAK2-positive essential thrombocythemia (ET) transformed to MPAL, and a patient with triple-negative primary myelofibrosis (PMF) (negative for JAK2, CALR, and MPL) transformed to ALL with subsequent lineage switch to AML.

scholarly journals Myeloid Neoplasms in the Guise of Nutritional Deficiency

2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Veda Parthasarathy
Keyword(s):  
Clinical Course ◽  
Myeloproliferative Neoplasms ◽  
Diagnostic Delay ◽  
Primary Myelofibrosis ◽  
Nutritional Deficiency ◽  
Vitamin B ◽  
Hematologic Neoplasms ◽  
Myeloid Neoplasms ◽  
High Prevalence ◽  
Iron Folic Acid

The classicBCR-ABL-negative myeloproliferative neoplasms (MPNs) which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are among the most frequent hematologic neoplasms. Because of their relatively smooth clinical course, it is likely that many of these MPNs actually go undetected. Considering the high prevalence of iron, folic-acid, and vitamin B12deficiencies in developing countries, their coexistence with MPN can be expected frequently. In such situations where both disorders coexist, MPN is often overlooked. This causes considerable diagnostic delay. In this paper, two cases of PMF and one case of PV where the diagnosis of MPN was delayed for about 3 years are discussed. Presence of concomitant vitamin B12, folate, and iron deficiencies perhaps camouflaged the underlying MPN. Bearing in mind the possibility of MPN, even in the setting of apparent nutritional deficiency and performing a bone marrow evaluation, is the crucial step in unveiling the hidden MPN.

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