Primary Myelofibrosis

Author(s):  
Wojciech Gorczyca
Author(s):  
JM Radley ◽  
SL Ellis

In effective thrombopoies is has been inferred to occur in several disease sates from considerations of megakaryocyte mass and platelet kinetics. Microscopic examination has demonstrated increased numbers of megakaryocytes, with a typical forms particularly pronounced, in primary myelofibrosis. It has not been documented if megakaryocyte ever fail to reach maturity in non-pathological situations. A major difficulty of establishing this is that the number of megakaryocytes normally present in the marrow is extremely low. A large transient increase in megakaryocytopoiesis can how ever be induced in mice by an injection of 5-fluorouracil. We have utilised this treatment and report here evidence for in effective thrombopoies is in healthy mice.Adult mice were perfused (2% glutaraldehyde in 0.08M phosphate buffer, pH 7.4) 8 days following an injection of 5-fluorouracil (150mg/kg). Femurs were subsequently decalcified in 10% neutral E.D.T.A. and embedded in Spurrs resin. Transverse sections of marrow revealed many megakaryocytes at various stages of maturity. Occasional megakaryocytes (less than 1%) were found to be under going degeneration prior to achieving full maturation and releasing cytoplasm as platelets. These cells were characterized by a peripheral rim of dense cytoplasm which enveloped a mass of organelles and vacuoles (Fig. 1). Numerous microtubules were foundaround and with in the organelle-rich zone (Fig 2).


Hematology ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 478-490
Author(s):  
Haotian Ma ◽  
Jincen Liu ◽  
Zilong Li ◽  
Huaye Xiong ◽  
Yulei Zhang ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Mariarita Spampinato ◽  
Cesarina Giallongo ◽  
Alessandra Romano ◽  
Lucia Longhitano ◽  
Enrico La Spina ◽  
...  

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hematopoietic stem-cell-derived clonal proliferation, leading to bone marrow (BM) fibrosis. Hematopoiesis alterations are closely associated with modifications of the BM microenvironment, characterized by defective interactions between vascular and endosteal niches. As such, neoangiogenesis, megakaryocytes hyperplasia and extensive bone marrow fibrosis, followed by osteosclerosis and bone damage, are the most relevant consequences of PMF. Moreover, bone tissue deposition, together with progressive fibrosis, represents crucial mechanisms of disabilities in patients. Although the underlying mechanisms of bone damage observed in PMF are still unclear, the involvement of cytokines, growth factors and bone marrow microenvironment resident cells have been linked to disease progression. Herein, we focused on the role of megakaryocytes and their alterations, associated with cytokines and chemokines release, in modulating functions of most of the bone marrow cell populations and in creating a complex network where impaired signaling strongly contributes to progression and disabilities.


Author(s):  
Mea Asou ◽  
Tomohiko Asakawa ◽  
Makoto Araki ◽  
Takashi Ehara ◽  
Tsunekazu Hishima ◽  
...  

Extramedullary hematopoiesis is widely known to occur in patients with primary myelofibrosis (PMF). Autopsy studies on individuals with PMF revealed that extramedullary hematopoiesis occurred in the kidneys in 35% of the cases, but there is little awareness regarding such lesions. A 63-year-old man was diagnosed with PMF based on a detailed examination of persistent high white blood cells. An examination of the patient’s medical records revealed an increased white blood cell count, deterioration of kidney function, and urinary protein excretion developed simultaneously. Thus, a kidney biopsy was performed. Advanced lymphocyte invasion was recognized in the interstitial tissue, and the tubular structure was highly disrupted. Based on these findings, he was diagnosed with interstitial nephritis. However, because of the large number of cells with nuclear atypia in the stroma, additional immunohistochemical staining was also performed, such as glycophorin A, naphthol AS-D, myeloperoxidase, and CD42b. As a result, invasion of three lineages of immature cells, erythroblasts, megakaryocytes, and granulocytes, was identified. Renal dysfunction resulting from interstitial cellular infiltration due to extramedullary hematopoiesis was therefore diagnosed. Treatment with ruxolitinib was initiated after a renal biopsy and the rate of decline in renal function was slightly reduced. Although, in myeloproliferative disorders, proliferative glomerular lesions are widely considered to be renal disorders, there is little awareness regarding interstitial lesions. Extramedullary hematopoiesis of the kidney in PMF is not uncommon, but 40% of cases are reportedly misdiagnosed as interstitial nephritis. Because extramedullary hematopoiesis can be controlled by ruxolitinib, early detection is important.


Author(s):  
Julian Baumeister ◽  
Tiago Maié ◽  
Nicolas Chatain ◽  
Lin Gan ◽  
Barbora Weinbergerova ◽  
...  

AbstractMyeloproliferative neoplasms (MPN), comprising essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are hematological disorders of the myeloid lineage characterized by hyperproliferation of mature blood cells. The prediction of the clinical course and progression remains difficult and new therapeutic modalities are required. We conducted a CD34+ gene expression study to identify signatures and potential biomarkers in the different MPN subtypes with the aim to improve treatment and prevent the transformation from the rather benign chronic state to a more malignant aggressive state. We report here on a systematic gene expression analysis (GEA) of CD34+ peripheral blood or bone marrow cells derived from 30 patients with MPN including all subtypes (ET (n = 6), PV (n = 11), PMF (n = 9), secondary MF (SMF; post-ET-/post-PV-MF; n = 4)) and six healthy donors. GEA revealed a variety of differentially regulated genes in the different MPN subtypes vs. controls, with a higher number in PMF/SMF (200/272 genes) than in ET/PV (132/121). PROGENγ analysis revealed significant induction of TNFα/NF-κB signaling (particularly in SMF) and reduction of estrogen signaling (PMF and SMF). Consistently, inflammatory GO terms were enriched in PMF/SMF, whereas RNA splicing–associated biological processes were downregulated in PMF. Differentially regulated genes that might be utilized as diagnostic/prognostic markers were identified, such as AREG, CYBB, DNTT, TIMD4, VCAM1, and S100 family members (S100A4/8/9/10/12). Additionally, 98 genes (including CLEC1B, CMTM5, CXCL8, DACH1, and RADX) were deregulated solely in SMF and may be used to predict progression from early to late stage MPN. Graphical abstract


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