Faculty Opinions recommendation of Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study.

Author(s):  
William Vainchenker
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 ◽  
...  

Biosensors ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 94
Author(s):  
Nirmita Dutta ◽  
Peter B. Lillehoj ◽  
Pedro Estrela ◽  
Gorachand Dutta

Cytokines are soluble proteins secreted by immune cells that act as molecular messengers relaying instructions and mediating various functions performed by the cellular counterparts of the immune system, by means of a synchronized cascade of signaling pathways. Aberrant expression of cytokines can be indicative of anomalous behavior of the immunoregulatory system, as seen in various illnesses and conditions, such as cancer, autoimmunity, neurodegeneration and other physiological disorders. Cancer and autoimmune diseases are particularly adept at developing mechanisms to escape and modulate the immune system checkpoints, reflected by an altered cytokine profile. Cytokine profiling can provide valuable information for diagnosing such diseases and monitoring their progression, as well as assessing the efficacy of immunotherapeutic regiments. Toward this goal, there has been immense interest in the development of ultrasensitive quantitative detection techniques for cytokines, which involves technologies from various scientific disciplines, such as immunology, electrochemistry, photometry, nanotechnology and electronics. This review focusses on one aspect of this collective effort: electrochemical biosensors. Among the various types of biosensors available, electrochemical biosensors are one of the most reliable, user-friendly, easy to manufacture, cost-effective and versatile technologies that can yield results within a short period of time, making it extremely promising for routine clinical testing.


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.


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