Subtypes Of Myeloproliferative Disorders Research Articles

The Prevalence of Myeloproliferative Disorders in A Group of Iraqi Patients And Its Relation To Blood Indices Parameters

AIM: The aim of this study was to measure the prevalence of myeloproliferative disorders in a sample of Iraqi patients and to measure the changes in patients’ blood parameters.
 BACKGROUND: Myeloproliferative disorders are a group of neoplasms affecting the bone marrow progenitor cells characterized by excess cells with a risk of transforming to acute leukemia. There is a gap in knowledge about the prevalence of Iraqi population. Thus, we investigated the prevalence and distribution of different types of myeloproliferative disorders in a sample of Iraqi patients.
 MATERIALS AND METHODS: Cross-sectional study is done at the National Center of Hematology from November 2019 till March 2020 on 75 patients who were diagnosed by a specialist hematopathologist to have one subtype of myeloproliferative disorders (MPDs). Blood samples were taken from them and analyzed to get complete blood count, blood film, bone marrow aspirate, and biopsy that were analyzed for each patient. Blood samples were taken from them and analyzed in terms of blood indices, which include red blood cells, white blood cells, and platelets.
 RESULTS: The 75 patients were found to be comprising 35 chronic myelogenous leukemia (CML) patients (46.7%), myelofibrosis 22 patients (29.3%), essential thrombocythemia (ET) 9 patients (12%), and polycythemia vera (PV) 9 patients (12%). In terms of male/female ratios, they were as follows: Myeloproliferative neoplasms (MPNs) male-to-female ratio is 1.2, CML= 0.94, myelofibrosis= 2.14 and ET= 0.5 and PV male-to-female ratio is 2.
 CONCLUSIONS : MPN male-to-female ratio in Iraq, which is 1.2, CML is the most common subtype. Regarding myelofibrosis, in our study, the male-to-female ratio is 2.14, which is much higher other countries. This could be attributed to high exposure to benzene and toluene which are well known to be causative agents for myelofibrosis. Regarding ET or PV, the male-to-female ratios were compatible with other countries.

Detection of the JAK2 V617F missense mutation by high resolution melting analysis and its validation

Background Janus kinase 2 (JAK2) is a tyrosine kinase involved in the cytokine signaling of several growth factors such as erythropoietin and thrombopoietin in normal and neoplastic cells. The G to T exchange at nucleotide 1849 in exon 14 of the JAK2 gene leads to a substitution of valine with phenylalanine at the amino acid position 617 (V617F) of the JAK2 protein. Currently, the occurrence of the JAK2 V617F mutation is well recognized in chronic myeloproliferative disorders (MPDs). Methods We identified JAK2 V617F missense mutation in patients with MPD by high resolution melting (HRM) analysis. HRM analysis is a new gene scan tool that quickly performs the PCR and identifies sequences alterations without requiring post-PCR treatment. This study included 7 PV patients (41.1%), 6 ET patients (35.3%), and 4 myelofibrosis patients (23.5%). Additionally, our methodology was compared with amplification refractory mutation system (ARMS) assay. Results Up to 5% of the JAK2 V617F mutation was successfully detected in patients with MPD using HRM analysis. Eleven out of 17 patients (64.7%) were positive for the presence of JAK2 V617F mutation. The prevalence of mutation in the different subtypes of MPDs was 85.7% in PV (6 of 7 patients), 66.7% in ET (4 of 6) and 5.9% in myelofibrosis (1 of 4). The results proved 100% comparable to those obtained by ARMS assay. Conclusions The HRM analysis is a rapid and effective technique for the detection of JAK2 V617F missense mutation.

Bone Marrow Histopathology in Myeloproliferative Disorders—Current Diagnostic Approach

Current diagnostic issues in chronic myeloproliferative disorders (MPDs) include the differentiation of essential thrombocythemia (ET) from its mimics: early (prefibrotic) stages of chronic idiopathic myelofibrosis (CIMF) and early polycythemia vera (PV), both of which can be associated with thrombocytosis. Applying a systematic evaluation of bone marrow histopathology, in accordance with the current World Health Organization (WHO) classification system, it is possible to identify cases of true ET as opposed to false ET, usually early-stage CIMF accompanied by an excess of platelets. This distinction is important because the frequency of complications such as progression to overt myelofibrosis, blastic crisis, and overall prognosis are significantly different in the two conditions. The diagnostic criteria of the Polycythemia Vera Study Group (PVSG) do not adequately define the initial stages of PV, nor do they distinguish PV with thrombocytosis from ET. Differentiation of the two is possible by bone marrow histopathology, which also is highly predictive (96%) in distinguishing PV from secondary polycythemia. In conclusion, bone marrow biopsy is an important diagnostic tool for distinguishing specific subtypes of MPD and should be a mandatory step for entry evaluation and follow-up of patients enrolled in prospective studies and/or clinical trials.

Clinical and morphological criteria for the diagnosis of prefibrotic idiopathic (primary) myelofibrosis.

A clinicopathological study was performed to define initial-prefibrotic precursor stages of idiopathic (primary) myelofibrosis (IMF) by presenting laboratory and histological bone marrow features. Contrary to the usually accepted diagnostic requirements for IMF, including bone marrow fibrosis and a leukoerythroblastic blood picture, we found that 80 patients did not completely comply with these criteria. In particular, this cohort displayed no increase in the reticulin-collagen fiber content of the bone marrow at onset. Therefore, these cases were occasionally regarded as unclassifiable chronic myeloproliferative disorders (MPDs), or presumptively as essential thrombocythemia (ET). Patients were characterized by a certain set of clinical parameters comprising a borderline to slight leukocytosis and therapy-refractory anemia, minimal to modest splenomegaly, and often an elevated platelet count. Peripheral blood films revealed, only very sparsely, tear drop cells and a few erythroid and myeloid precursors, but no definite leukoerythroblastic reaction. Bone marrow histopathology was consistent with an increase in cellularity and a prominent left-shifted neutrophil granulopoiesis. Erythropoiesis disclosed a slight reduction with small to medium-sized islets. Megakaryopoiesis was the most prominent diagnostic hallmark to distinguish initial-prefibrotic IMF from the allied subtypes of MPDs. This cell lineage was not only characterized by a conspicuous growth and abnormal clustering, but also by a pronounced deviation from nuclear-cytoplasmic differentiation (dysplastic appearance). Cytological anomalies were compatible with a large variety of size and shape, ranging from giant- to atypical micromegakaryocytes with compact and bulky, cloud-like nuclei, due to a coarse lobulation and a frequent occurrence of naked (denuded) nuclei. Follow-up examinations, including sequential trephine biopsies in 22 patients, revealed a transition into myelofibrosis accompanied by laboratory findings in keeping with manifest IMF. In conclusion, morphological and clinical parameters have been validated by this study, which are consistent with a set of diagnostic criteria to recognize initial or prefibrotic precursor stages of IMF.

Clinicopathology and histochemistry on bone marrow biopsies in chronic myeloproliferative disorders – a clue to diagnosis and classification

A clinicopathological study was carried out to address the currently still controversial issues of: 1) thrombocythaemias in chronic myeloproliferative disorders (MPDs); 2) initial, prefibrotic idiopathic myelofibrosis (IMF); 3) discrimination of spurious polycythaemic states or polyglobuly (PG) from polycythaemia vera (PV); 4) unclassifiable MPDs. Based on a synoptical approach which implicates a comparative evaluation of laboratory data and histopathology of the bone marrow, the discriminating efficiency of both diagnostic tools has been emphasized. An elaborate evaluation of histotopography and cytological appearence of megakaryopoiesis is an invaluable aid to distinguish the different subtypes of MPDs which may eventually present with a significant elevation of the platelet count. Prefibrotic IMF is not only associated with a certain set of clinical symptoms (minimal to slight anaemia, splenomegaly, thrombocytosis), but should also be characterized by specific alterations of bone marrow morphology. Moreover, follow-up studies are in keeping with the finding that these patients evolve into typical IMF regarding laboratory parameters and ensuing myelofibrosis. Smokers polycythaemia – PG may be separated from early PV by the significant raise in the red cell mass and also by a few, easily determinable clinical parameters (i.e. EPO level, thrombocytosis, LAP). Both conditions can be distinguished by regarding bone marrow features (megakaryopoiesis, interstitial changes) which exert a distinctive impact. According to our experience the majority of patients categorized as unclassifiable MPDs include cases in which clinical or morphological data are inadequate to permit a more precise diagnosis. Only in a small proportion not a failing methodology, but initial stages of the disease process requires sequential examinations to reach a correct diagnosis.

Histochemistry and morphometry on bone marrow biopsies in chronic myeloproliferative disorders - aids to diagnosis and classification.

The aim of this review is to evaluate morphological characteristics of the different subtypes of chronic myeloproliferative disorders (MPDs) derived by applying immunohistochemical and morphometric techniques to bone marrow biopsies and to combine these results with relevant clinical parameters. In comparison to control specimens, a significant decrease in erythroid precursors is determinable in chronic myeloid leukemia (CML), while this cell lineage is most prominent in polycythemia vera (PV) and moderately to markedly reduced in idiopathic myelofibrosis (IMF). On the other hand, neutrophilic granulopoiesis shows a predominance in CML and a relevant increase in PV, but no conspicuous changes are detectable in essential thrombocythemia (ET). CML is characterized by a prevalent growth of dwarflike micromegakaryocytes, occurring in particular in the so-called megakaryocyte-rich subtypes (about 30%). This finding differs significantly from the pleomorphous aspect, i.e. , clusters of small to giant-sized megakaryocytes in PV and the grossly abnormal (dysplastic) appearance of this cell lineage in patients with IMF. Similar cytological abnormalities of megakaryopoiesis consistent with maturation defects are never encountered in ET. The incidence of mature (resident) macrophages (phagocytic reticular cells) is significantly enhanced in IMF in comparison to the other MPDs and controls. Moreover, there is a striking difference in the density of reticulin-collagen fibers, ranging from normal (ET) to extreme values (IMF). In IMF more than 80% of the patients present with some degree of myelofibrosis-osteosclerosis at diagnosis, while the rest show an initial prefibrotic, hypercellular stage. This feature deserves special attention since, when accompanied by thrombocythemia, it may simulate ET. Sequential bone marrow biopsies in patients with IMF disclose that evolution of myelofibrosis is progressive, but occurs at a variable and unpredictable speed. A synoptical approach regarding clinical diagnosis and histological subtyping of MPDs is explicitly recommended and demonstrated by sets of diagnostic criteria. This rationale requires equal consideration of laboratory data and morphology by clinicians to include well-defined subtypes of MPDs into prospective management studies. Furthermore, it may even warrant follow-up studies and repeated bone marrow examinations in initially unclassifiable cases.

Clinicopathological Diagnosis and Differential Criteria of Thrombocythemias in Various Myeloproliferative Disorders by Histopathology, Histochemistry and Immunostaining from Bone Marrow Biopsies

Differentiation of essential thrombocythemia (ET) from thrombocythemias occurring in various subtypes of chronic myeloproliferative disorders (MPDs) is controversial, because of the lack of uniform clinical and morphological criteria. A retrospective clinicopathologic study was performed on 375 patients presenting with a MPD and a platelet count exceeding 500 × 109/1. For comparison 35 patients with reactive thrombocytosis (RT) and five patients with a myelodysplastic syndrome (MDS-5q-syndrome) were enrolled into this study. In addition to a complete clinicopathological work-up, procedures included histochemical and immunological staining techniques and morphometry of bone marrow biopsies for proper evaluation of megakaryocytes (CD61) and erythroid precursors (Ret40f). Because of the high patient's age on admission, relative survival rates with corresponding disease-specific loss of life expectancy were calculated. Analysis of clinical and morphological characteristics, in particular megakaryopoiesis revealed features which enabled a clear-cut distinction between thrombocythemias in MPDs and thrombocythemic states in MDS. This rationale proved to be most important for the diagnostic discrimination of the 33 patients with initial (prefibrotic) stages of idiopathic myelofibrosis (IMF) from ET (40 patients). A new set of relevant criteria for the diagnosis of IMF with special regard to early stages and its distinction from ET has been proposed. Hemorrhagic episodes were more frequently observed in ET than in thrombocythemias associated with polycythemia vera (PV). Computation of specific loss of life expectancy revealed two extremes: thrombocythemia in CML (81%) and ET (3%), whereas thrombocythemias in PV and IMF did not show a significantly different life loss (19–22%). The revised criteria for ET, PV and IMF are reliable by taking histopathological features from bone marrow biopsies into consideration, particularly for the diagnosis of ET and its differentiation from thrombocythemias as a presenting symptom accompanying the various subtypes of MPDs.