CEL, NOS), is a leukemia-inducing disorder in the eosinophil cell lineage that causes eosinophil blood counts greater than 1,500/μL. The most recent (2017) World health organization criteria specifically excludes from this disorder hypereosinophilia/eosinophilia associated with BCR-ABL1 fusion gene-positive chronic myeloid leukemia, polycythemia vera, essential thrombocytosis, primary myelofibrosis, chronic neutrophilic leukemia, chronic myelomonocytic leukemia, atypical chronic myelogenous leukemia, clonal eosinophilias involving gene rearrangements of PDGFRA, PDGFRB, or FGFR1, and chromosome translocations that form PCM1-JAK2, ETV6-JAK2, or BCR-JAK2 fusion genes. For this diagnosis, immature eosinophil (e.g. myeloblast) cell counts in the bone marrow and peripheral blood must be less than 20% and the chromosomal alterations (inv(16)(p13.1q22)) and t(16;16)(p13;q22) as well as other features diagnostic of acute myelogenous leukemia must be absent. The latter diagnostic features include clonal cytogenetic abnormalities and molecular genetic abnormalities diagnostic for other forms of leukemia or the presence of myeloblast counts greater than 55% in bone marrow or 2% in blood. Chronic eosinophilic leukemia may transform into acute eosinophilic or other types of acute myelogenous leukemia. Familial eosinophilia
Familial eosinophilia is a rare congenital disorder characterized by the presence of sustained elevations in blood eosinophil levels that reach ranges diagnostic of eosinophilia or, far more commonly, hypereosinophilia. It is an autosomal dominant disorder in which genetic linkage gene mapping family studies localize the gene responsible for it to chromosome 5 at position q31–q33, between markers D5S642 and D5S816.
Elevations in blood eosinophil counts can be transient, sustained, recurrent, or cyclical.Eosinophil counts in human blood normally range between 100 and 500 per/μL. Maintenance of these levels results from a balance between production of eosinophils by bone marrow eosinophil precursor cells termed CFU-Eos and the emigration of circulating eosinophils out of the blood through post-capillary venules into tissues. Eosinophils represent a small percentage of peripheral blood leucocytes (usually less than 8%), have a half-life in the circulation of only 8–18 hours, but persist in tissues for at least several weeks.Eosinophils are one form of terminally differentiated granulocytes; they function to neutralize invading microbes, primarily parasites and helminthes but also certain types of fungi and viruses. They also participate in transplant rejection, Graft-versus-host disease, and the killing of tumor cells. In conducting these functions, eosinophils produce and release on demand a range of toxic reactive oxygen species (e.g. hypobromite, hypobromous acid, superoxide, and peroxide) and they also release on demand a preformed armamentarium of cytokines, chemokines, growth factors, lipid mediators (e.g. leukotrienes, prostaglandins, platelet activating factor), and toxic proteins (e.g. metalloproteinases, major basic protein, eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin). These agents serve to orchestrate robust immune and inflammatory responses that destroy invading microbes, foreign tissue, and malignant cells. When overproduced and over-activated, which occurs in certain cases of hypereosinophilia and to a lesser extent eosinophilia, eosinophils may misdirect their reactive oxygen species and armamentarium of preformed molecules toward normal tissues.