Hypokalemia due to renal potassium loss has frequently been observed in patients with acute myeloid leukemia (AML). The pathogenic mechanism for this hyperkaluresis is unclear. In this report we describe a patient with AML FAB M4, in whom the clinical course, the electrolyte disturbances, the serum aldosterone levels, and the diffuse hyperplasia of the adrenal cortex documented a typical case of marked secondary hyperaldosteronism. On analysis of the leukemic cells of this patient compared with normal bone marrow cells, a significant increase of renin-like activity in the cytosol of the blast cells was noted. Activation of the renin-angiotensin-aldosterone system by paraneoplastic production of renin-like activity in AML blast cells might contribute to the hypokalemia often observed in patients with acute myeloid leukemia.

Summary. The biological mechanisms responsible for the association of specific karyotypes with prognosis in acute myeloid leukaemia (AML) remain largely unclear. A prospective study was performed to evaluate how far cytogenetically defined prognostic subgroups of AML differ in their proliferative activity as a potential mechanism for differential sensitivities to S-phase-specific induction chemotherapy comprising cytosine arabinoside (AraC). One hundred and eighty-seven patients with de novo AML were included in the study; 25 patients with a favourable [inv(16), t(8;21), t(15;17)] karyotype, 99 with a normal karyotype, 29 with an unfavourable karyotype (25, 5q±, 27, 7q±, complex aberrations) and 34 with cytogenetic aberrations of unknown prognostic significance (all others). The favourable group demonstrated the highest ex vivo proliferative activity (PA) (3´41 pmol/10 5 cells), significantly (P 0´02) exceeding the unfavourable group with the lowest PA (0´72) and the group with a normal karyotype (1´06) or with karyotype of unknown significance (1´05) that both demonstrated an intermediate PA.Samples with a high PA (. median of the whole group) were more likely to produce interleukin 3, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF) (56%, 43% and 50%) than cells with a low PA (33%, 36% and 36%; n.s.). The effect of priming by exogenous GM-CSF or G-CSF was significantly more pronounced in samples with a low PA than in rapidly proliferating samples (P , 0´01). For the whole group, a high PA was closely associated with an increased incorporation of AraC triphosphate (AraCTP) into the DNA (P , 0´0001). Clinically, a high PA was associated with a better complete remission (CR) rate in the normal (95% versus 62%) and the unfavourable group (75% versus 33%). The significant differences in proliferative activity between cytogenetic subgroups of AML are associated with increased cytosine arabinoside pharmacodynamics and constitute one potential mechanism for the different response of cytogenetic subgroups to AraC-based induction therapy.

Summary.Hypokalaemia is a clinical phenomenon in patients with acute myeloid leukaemia (AML) to which activation of the renin-angiotensin system (RAS) may contribute. Recently monocytes were found to express renin, the key initializing enzyme of the RAS. By RT/PCR, transcripts for renin were detected in four of 18 bone marrow samples from patients with AML. Three leukaemic cell lines, isolated monocytes, bone marrow stromal cells and 25 peripheral blood and 24 bone marrow samples of normal controls were negative for renin transcripts. In view of the importance of local RAS in other tissues, the expression of renin in the bone marrow of AML patients warrants further investigation.

An increased plasma cell count in the bone marrow occurs in a subgroup of patients with acute myeloid leukemia (AML). The pathogenic mechanism for this plasmacytosis is unclear. In this report we describe two patients with AML and plasmacytosis who shared some features of their diseases. The morphological subtypes were AML M4 and M4eo; the leukemias were secondary to cytotoxic pretreatment, and complex cytogenetic changes were found in the leukemic cells of both patients. There was a marked increase in the number of bone marrow plasma cells in both cases and no monoclonal immunoglobulin was detectable. The IgH-CDR3 gene scan depicted a monoclonal IgH rearrangement in the bone marrow cells of one patient. Analysis of the cytokine production of the leukemic cells showed a high production of IL-6 of the leukemic blast cells in the in vitro cell culture and a high cytoplasmic IL-6 in the leukemic cells as revealed by immunocytology. We describe the clinical picture of a type of secondary AML with FAB M4 morphology associated with bone marrow plasmacytosis. We suggest that paracrine growth stimulation of plasma cells by paraneoplastic IL-6 production of the leukemic blast cells contributes to the plasmacytosis observed in patients with AML.

The current study was undertaken to search for differences in the biology of cytogenetic subgroups in patients with de novo acute myeloid leukemia (AML). In addition, factors influencing the metabolism of cytosine arabinoside (araC) as the key agent of antileukemic activity were assessed. Bone marrow aspirates from 91 patients with newly diagnosed AML in whom karyotypes were successfully obtained were analyzed: (1) for spontaneous proliferative activity by 3 H-thymidine ( 3 H-TdR) incorporation; (2) proliferative response to GM-CSF by in vitro incubation of blasts for 48 h with or without GM-CSF (100 U/ml) followed by an additional 4-h exposure to 3 H-TdR (0.5 Ci/ml); and (