From the Guidelines
The diagnosis of primary myelofibrosis (PMF) should be based on the revised WHO criteria, which requires meeting all 3 major criteria and 2 minor criteria, as outlined in the study by 1. To diagnose PMF, the following major criteria must be met:
- Presence of megakaryocyte proliferation and atypia, usually accompanied by either reticulin and/or collagen fibrosis, or, in the absence of significant reticulin fibrosis, the megakaryocyte changes must be accompanied by an increased bone marrow cellularity characterized by granulocytic proliferation and often decreased erythropoiesis
- Not meeting WHO criteria for PV, CML, MDS, or other myeloid neoplasm
- Demonstration of JAK2^617V^F or other clonal marker, or in the absence of a clonal marker, no evidence of bone marrow fibrosis due to underlying inflammatory or other neoplastic diseases Additionally, at least 2 of the following minor criteria must be present:
- Leukoerythroblastosis
- Increase in serum lactate dehydrogenase level
- Anemia
- Palpable splenomegaly As noted in the study by 1, the distinction between PMF and other myeloid neoplasms, such as MDS with fibrosis, ET, or acute panmyelosis with myelofibrosis, requires careful morphologic assessment. The use of these criteria, as outlined in the study by 1, allows for accurate diagnosis and differentiation of PMF from other myeloid neoplasms, which is essential for determining the appropriate treatment approach and improving patient outcomes.
From the Research
Ischemic Preconditioning
- Ischemic preconditioning is a phenomenon where brief episodes of ischemia/reperfusion applied prior to a longer coronary artery occlusion reduce myocardial infarct size 2, 3, 4
- This phenomenon is mediated by activation of adenosine, bradykinin, opioid and other receptors, with subsequent activation of intracellular mediators leading to mitochondrial protection 2
- Preconditioning mimetic agents that stimulate the biochemical pathways of ischemic preconditioning and protect the heart without inducing ischemia have been examined in numerous experimental studies 3
Postconditioning
- Postconditioning refers to repetitive short-lived cycles of ischemia-reperfusion applied after the index ischemia, which shares a common pathway with preconditioning and is more useful and relevant in clinical practice 2, 3
- Postconditioning is dependent on complex signalling pathways involving ligands released from ischaemic myocardium, G-protein-linked receptors, membrane growth factor receptors, phospholipids, signalling kinases, NO, PKC and PKG, mitochondrial ATP-sensitive potassium channels, reactive oxygen species, TNF-α and sphingosine-1-phosphate 5
- The final effector is probably the mitochondrial permeability transition pore and the signalling produces protection by preventing pore formation 5
Clinical Application
- Despite the huge interest and the great body of evidence that verify the effectiveness of conditioning, clinical application has remained limited due to controversies over the appropriate intervention protocol, but also interference of medication, comorbidities and other factors that may enhance or blur the protective effect 2, 3
- Recent clinical trials such as AMISTAD I and II suggest that some preconditioning mimetics may reduce myocardial infarct size when given along with reperfusion or, as in the IONA trial, have benefit on clinical events when administered chronically in patients with known coronary artery disease 3
- It is possible that some of the benefit described for adenosine in the AMISTAD 1 and 2 trials represents a manifestation of the recently described postconditioning phenomenon 3