[Treatment of myelodysplastic syndrome and acute myelogenous leukemia with vitamin D3 [1 alpha(OH)D3]].
It is known that 1 alpha, 25(OH)2D3 is an inducer of nonlymphoid leukemic cell differentiation to monocyte-macrophage-like in vitro. The effects of oral administration of 4.5-15 micrograms/d 1 alpha (OH)D3, which is converted to 1 alpha, 25(OH)2D3 in vivo by liver cells, on leukemic cells were studied in two patients with AML and one with RAEB. In these three cases, 1 alpha (OH)D3 reduced the number of leukemic cells in the bone marrow and aggregated the dispersed chromatin of leukemic cells as heterochromatin. Furthermore, this drug induced atypical lymphocyte-like cells, which were considered to be differentiated from leukemic cells in case 1, and improvement of pancytopenia in case 3. While hypercalcemia developed during 1 alpha (OH)D3 therapy in case 1, it disappeared within three days after discontinuation. We also studied the in vitro effects of 1 alpha, 25 (OH)2D3 on leukemic cells freshly isolated from the bone marrow in these three cases. After incubation with 10(-8) M 1 alpha, 25(OH)2D3 at 37 degrees C for 72 h, the number of adherent cells on the bottom of Petri dishes had increased. These cells were quite similar to monocyte-macrophages. These leukemic cells, after differentiation induced by 1 alpha, 25(OH)2D3, reacted strongly with monoclonal antibodies My-4 and My-7. Both 100 microM D-cis and L-cis diltiazem (calcium channel blocker) enhanced the differentiation of HL-60 cells induced by 1 alpha, 25 (OH)2D3. There was no significant difference between D-cis and L-cis diltiazem with regard to this enhancing effect. The cytoplasmic free Ca2+ concentration in HL-60 cells induced by 1 alpha, 25(OH)2 D3 and/or diltiazem, was increased significantly as compared with that in HL-60 cells incubated without inducers.
Irino
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S
1st Dept. of Internal Medicine, Kagawa Medical School.
Taoka
T
T
D000284:Administration, Oral; D000368:Aged; D000754:Anemia, Refractory, with Excess of Blasts / Q000097:blood / Q000188:drug therapy; D002118:Calcium / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects; D002762:Cholecalciferol / Q000008:administration & dosage / Q000627:therapeutic use*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy*
D002762:Cholecalciferol; D004110:Diltiazem; D002118:Calcium