Two cases of spontaneous remission in acute promyelocytic leukemia are reported. They had precedent febrile episodes and subsequent resolution of all clinical and hematological abnormalities occurred after supportive care including administration of various antibiotics. Their remissions lasted for 12 and five months respectively, when they relapsed.
Adult ; Female ; Humans ; Leukemia, Promyelocytic, Acute/*physiopathology ; Male ; Remission, Spontaneous

OBJECTIVETo evaluate the effect of tetra-arsenic tetra-sulfide (As4S4) therapy on the corrected QT interval (QTc) in the acute promyelocytic leukemia (APL) patients.

METHODSNinety cases of APL treated with As4S4 were divided into two groups--the remission induction group and maintenance therapy group. Blood arsenic concentration was measured and a 12-lead electrocardiogram (ECG) was simultaneously performed before treatment and after remission in the induction group, and before and 2, 4, 6, 8, 10 courses after the treatment in the maintenance therapy group. QT interval on each ECG was measured and corrected by the Bazett formula.

RESULTSOral administration of As4S4 could lead to the prolongation of QTc both in remission induction and maintenance therapy groups. QTc prolongation was related to the doses of As4S4 and blood arsenic levels. QTc prolongation and its variation range were increased with accumulative doses of As4S4 and the blood arsenic levels. In ten courses maintenance therapy patients, the average abnormal rate of QTc was 37.7%. Blood arsenic concentration was increased slowly with courses, but the variation had no statistical difference (P > 0.05). All the patients whose QTc was abnormal (> or = 440 ms) had neither symptoms nor serious cardiac events, such as ventricular tachycardia and Torsade de pointes and could complete the As4S4 therapy.

CONCLUSIONAlthough As4S4 therapy can lead to QTc prolongation in the treatment of APL patients, it does not preclude the completion of the therapy.

Adolescent ; Adult ; Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Electrocardiography ; drug effects ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; physiopathology ; Male ; Middle Aged ; Sulfides ; pharmacology

Arsenic trioxide (As2O3, ATO) is a recently developed drug for the effective treatment of acute promyelocytic leukemia (APL). Experimental studies showed that in vitro differentiation-inducing ability on APL cells of this drug is not significant compared with its in vivo activity. We unexpectedly found recently that hypoxia-mimetic agents and moderate real hypoxia triggered acute myeloid leukemic cells to undergo differentiation. Furthermore, intermittent hypoxia significantly prolonged the survival of the transplanted leukemic mice with inhibition of infiltration and induction of differentiation of leukemic cells. In the following works, molecular mechanisms of hypoxia-induced differentiation were investigated and some interesting results have been obtained. This review will shortly summarize the related progresses and discuss the questions remained to be further investigated.
Animals ; Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Cell Transformation, Neoplastic ; drug effects ; Humans ; Hypoxia ; physiopathology ; Hypoxia-Inducible Factor 1, alpha Subunit ; pharmacology ; Leukemia ; drug therapy ; pathology ; Leukemia, Promyelocytic, Acute ; drug therapy ; pathology ; Oxides ; therapeutic use

OBJECTIVETo study the fibrinolytic activity in patients with acute promyelocytic leukemia (APL) and its alteration in all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) treatment.

METHODSPlasma fibrinogen concentration was determined with the conventional method, and the levels of fibrin degradation products (FDP) and D-dimer were quantified with ELISA. Plasminogen was measured by chromogenic assay. Cell surface expression of Annexin II and u-PAR and their mRNA levels were measured by flow cytometry and real time-PCR, respectively.

RESULTSThe levels of FDP and D-dimer in APL were remarkably higher in APL patients than that in normal controls, while fibrinogen and plasminogen were lower. Both Annexin II and u-PAR were highly expressed on APL cells, which declined after treatment with ATRA and/or ATO, but remained higher than those on normal bone marrow mononuclear cells.

CONCLUSIONAbnormally high levels of Annexin II and u-PAR expression on APL cells may contribute to the increased production of plasmin, leading to primary hyperfibrinolysis in APL. ATRA and ATO therapy induces down-regulation of Annexin II and u-PAR expression, which may be contribute, at least in part, to the relief of the hemorrhagic complications in APL.

Adolescent ; Adult ; Aged ; Annexin A2 ; analysis ; Arsenicals ; therapeutic use ; Female ; Fibrinolysis ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; physiopathology ; Male ; Middle Aged ; Oxides ; therapeutic use ; RNA, Messenger ; genetics ; Tretinoin ; therapeutic use ; Urokinase-Type Plasminogen Activator ; analysis ; Young Adult

OBJECTIVETo study the molecular mechanism of tetramethylpyrazine to induce human promyelocytic HL-60 leukemia cells differentiation.

METHODThe cell proliferation was determined by MTT. The differentiation of the cells was detected by NBT reduction test. Cellular morphology was observed by Wright's staining. Cell cycle distribution and the distribution of CD11b, CD14 were detected by flow cytometry. Then RT-PCR and Western blot assay were employed to detect the expressions of c-myc, p27, CDK2 and cyclinE1 in HL-60 cells after exposure to TMP.

RESULTTMP inhibited the proliferation in a dose and time dependent manner. TMP at the concentration of 200 mg x L(-1) to 300 mg x L(-1) induced unterminal differentiation of HL-60 cell and synergistically blocked the cell cycle progression of HL-60 cells in G0/G1 phase. The expression of c-myc was down-regulated as well as the protein expression of cyclin E and CDK2, while the mRNA and protein expression of P27 were remarkably up-regulated.

CONCLUSIONSmall doses of TMP induces differentiation of HL-60 cells throughout the cell cyde, as detected by a slower rate of accumulation in G0/G1, possibly by regulating the expression and activity of G1/S phase-related molecules.

Cell Cycle Proteins ; genetics ; metabolism ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Gene Expression Regulation, Leukemic ; drug effects ; HL-60 Cells ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; metabolism ; physiopathology ; Pyrazines ; pharmacology

BACKGROUNDMost patients with acute myelogenous leukemia (AML) suffer from disordered hemostasis. We have previously shown that annexin II (Ann II), a high-affinity co-receptor for plasminogen/tissue plasminogen activator, plays a central role in primary hyperfibrinolysis in patients with acute promyelocytic leukemia (APL). The expression of Ann II in cells from patients with major subtypes of AML and the effect of arsenic trioxide (As2O3) on Ann II expression in AML cells were investigated to determine whether As2O3-mediated downregulation of Ann II could restore hemostatic stability.

METHODSA total of 103 patients (48 females and 55 males; age, 19 - 58 years) were included. Plasma samples were collected before and after treatment as well as after complete remission. Ann II and plasminogen activation were measured in leukemic cells during treatment with 1 micromol/L As2O3.

RESULTSBefore As2O3 treatment, Ann II mRNA expression (real-time PCR) was the highest in M3 cells (P < 0.05), higher in M5 cells than that in M1, M2, M4, and M6 cells (P < 0.001), and positively correlated with Ann II protein expression (flow cytometry) (r = 0.752, P < 0.01). Exposure for up to 120 hours to As2O3 (1 micromol/L) had no significant effect on Ann II protein in M1 and M2 leukemic cells, but decreased Ann II protein expression twofold within 48 hours of exposure in M3 cells (P < 0.05) and twofold within 96 hours in M5 cells (P < 0.05). The rate of plasmin generation was higher in APL, M5, and M4 cells than in M1, M2, and M6 cells.

CONCLUSIONSAs2O3 may reduce hyperfibrinolysis in AML by downregulation of Ann II. Furthermore, As2O3 affects more than one form of AML (APL, M4 and M5), suggesting its potential role in their management.

Adult ; Annexin A2 ; metabolism ; Arsenicals ; pharmacology ; Bone Marrow Cells ; cytology ; drug effects ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Down-Regulation ; drug effects ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism ; physiopathology ; Male ; Middle Aged ; Oxides ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult