signs, hematological abnormalities, and specialized laboratory findings seen in ds-amkl. these children should bear one or more of the genetic aberrations associated with the disease but not the inactivating gata1 mutations, extra copies of chromosome 21 genes, or other genetic abnormalities associated with ds-amkl. non-ds-amkl has many clinical and laboratory features similar to and must be distinguished from acute panmyelosis with myelofibrosis, a disorder characterized by bone marrow fibrosis, abnormal megakaryocytes, macrocytic erythropoiesis, defects in neutrophil production, reduced blood levels of most circulating cells (i.e. pancytopenia), and low levels of circulating blast cells. analyses of circulating and bone marrow blast cells for features of amkl (see diagnosis section of ds-amkl) and genetic aberrations is helpful in distinguishing the two diseases. treatment in a review of 153 patients treated for non-ds-amkl between 1990 and 2014 with various intensive chemotherapy protocols that included cytarabine, an anthracycline (e.g. daunorubicin, doxorubicin), and in 25% of cases human stem cell transplantation, the probability of overall 4 year survival rate, probability of 4 year event-free survival, and probability of 4 year cumulative relapse rate were 56, 51, and 29%, respectively. a more recent treatment regimen that is similar to that used to treat ds-amkl as described above (except it employs the high dose of cytarabine used to treat aml) gives better results and has been recommended for non-ds-amkl. the response to this regimen approached that seen in non-ds-amkl, i.e. its complete remission and estimated 10 year survival rates were both 76%. similar to ds-amkl treatment regimens, allogenic rather than autologous stem cell bone marrow transplantation should be considered in non-ds-amkl cases that have relapsed following their first chemotherapy-induced complete remission. further studies may indicate that this recent cancer chemotherapy regimen plus allogenic bone marrow transplantation in cases which relapse after the first remission are the preferred treatment for non-ds-amkl. prognosis in a review of 153 patients treated for non-ds-amkl between 1990 and 2014 with various intensive chemotherapy protocols that included cytarabine, an anthracycline (e.g. daunorubicin, doxorubicin), and in 25% of cases human stem cell transplantation, the probability of overall 4 year survival rate, probability of 4 year event-free survival, and probability of 4 year cumulative relapse rate were 56, 51, and 29%, respectively. patients with non-ds-amkl given the treatment regimen described for ds-amkl above had a much better prognosis than patients treated with earlier-devised treatment regimens: their overall survival rate using these regimen was estimated to be 76%. adult-amkl pathophysiology adult-amkl can result from the progression of other myeloproliferative neoplasms (mpn) viz., chronic myelogenous leukemia, polycythemia vera, essential thrombocytosis, and primary myelofibrosis. in one review of adult-amkl, 25% of 49 cases were considered as secondary to one of these mpn. the mechanism behind these cases of secondary amkl are unknown although an inversion in chromosome 3 at positions q21 and q26, i.e. inv(3)(q21q26), is often seen in these secondary cases of adult-amkl. rare cases of adult-amkl also have mediastinal germ cell tumors. these tumors are malignancies of germ cells, i.e. primitive cells that give rise to sperm and ovum cells. in adult-amkl, mediastinal germ cell tumors that are associated with adult-amkl are not seminomas (i.e. do not originate from the sperm cell line) and occur before or concomitantly with but not after the diagnosis amkl is made. the three most common genetic aberrations in the bone marrow cells of these individuals (representing ~65% of all cases) were inversions in the p arm of chromosome 12, trisomy 8, and an extra x chromosome. in several of these cases, the genetic aberrations in the malignant platelet precursor cells were similar to those in the malignant mediastinal germ cells. these results and those of other analyses suggest that the two malignancies derive from a common founding clone of cells (i.e. a set of genetically identical cells). overall, the most common genetic aberrations occurring in adult-amkl are the previously described inv((3)(q21q26) inversion, translocation between the q arm of chromosome 9 at position 34 and the q arm of chromosome 22 at position 11, i.e. (t(9:22)(q34:q11), and various aberrations in chromosome 5 or chromosome 7. aberrations in the latter two chromosomes are also commonly seen in an aml that is associated with myelodydplastic-related changes (i.e. predominance of immature blood cells in the bone marrow). the underlying malignancy-causing mechanism, if any, behind these genetic aberrations requires further study. presentation adult-amkl may occur in individuals who have a prior diagnosis of and/or present with chronic myelogenous leukemia, polycythemia vera, essential thrombocytosis, primary myelofibrosis, or mediastinal germ cell tumor. amkl associated with mediastinal germ cell tumors typically occurs in younger adults, i.e. ages 13–36 (average age 24). cases occurring in children aged ≤18 years, which represent ~20% of all cases, could be regarded in the non-ds-amkl category. cases of the disease not associated with mediastinal germ cell tumors occur in adults who as a group have older median age centering around those 50–70 years old. the disorder is far more fulminant than non-ds-amkl and ds-amkl and generally presents with more serious hematological symptoms (e.g. anemia-related) and a much higher incidence of extramedullary manifestations (e.g. organ enlargement, leukemia cutis) than seen in the other two forms of amkl. diagnosis adult-amkl commonly occurs in adults in their sixties and seventies but may be seen in adolescents as young as 13. its diagnosis can be suspected in cases that have either a prior history of mpn or a history or current findings indicating the presence of mediastinal blast cell tumor. in all cases, the diagnosis adult-amkl rests upon the same determinations used to diagnose ds-amkl, e.g. increased blast cells in blood and/or bone marrow, immunochemical evidence that these blast cells bear platelet line-specific markers, and occurrence of the genetic aberrations in these blast cells that have been associated with the disease. treatment adult-amkl has remained poorly responsive to the treatment regiments used in ds-amkl and non-ds-amkl. these treatments have given complete remission rates of 43-50%. prognosis the prognosis of adult-amkl in patients treated for the disease is far below that of other forms of amkl. their median overall survival times are only 18 to 41 weeks with 5 year survival rates of only 10-11 percent. major improvements in these statistics will likely require new approaches directed at the underlying mechanisms driving the disease.