OBJECTIVETo investigate the effect of homoharringtonine (HHT) on leukemic stem-like cells (LSC) in human acute myeloid leukemia (AML) cell lines.

METHODSThe phenotypes of AML cell lines U937,Kasumi-1,and KG-1 cells were analyzed by flow cytometry (FACS). The effect of HHT on leukemia stem-like cells with immunophenotype of CD34(+)CD38(-)CD96(+) was detected with FACS. Cell growth was measured by MTT assay. Activation of Caspase pathway and expression of apoptosis-related regulator proteins were examined by Western blotting.

RESULTSFACS demonstrated that the 69% of KG-1 cells expressed LSC phenotype CD34(+)CD38(-)CD96(+), while 26.7% on Kasumi-1 cells expressed this marker. In contrast,U937 cells showed CD96 negative. HHT significantly inhibited cell growth of KG-1 cells with an IC(50) of 16.9 ng/ml at 48 h. The ratio of CD34(+)CD38(-)CD96(+) cells decreased from 63.6% to 17.1% after HHT treatment. Enhanced apoptosis was demonstrated in HHT group evidenced by strong activation of Caspase-9,Caspase-3 and PARP.HHT treatment resulted in down-regulation of expression of anti-apoptotic protein BCL-2 and phosphorylated-Akt.

CONCLUSIONHHT can effectively kill the leukemic stem-like cells in human AML cell line KG1 by inhibiting cell growth and inducing apoptosis which is associated with activation of Caspase pathway and down-regulation of anti-apoptotic proteins and phosphorylated-Akt.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Gene Expression Regulation, Neoplastic ; Harringtonines ; pharmacology ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Neoplastic Stem Cells ; drug effects ; metabolism ; pathology

OBJECTIVETo explore the expression and clinical significance of ID1 gene in acute myeloid leukemia (AML) patients.

METHODReal-time quantitative PCR (RQ-PCR) was used to test the expression level of ID1 gene in 114 de novo adult AML patients, and the clinical features of these patients were analyzed.

RESULTSID1 gene transcript levels were detectable in BM mononuclear cells from 114 patients with AML, the median expression level of all samples was 8525 (range: 57 - 11 233 238). There was a statistically significant difference on expression level of ID1 gene among the three different cytogenetic prognosis groups, and the poor prognosis group (median: 36 840, range: 336 - 11 233 238) harbored the significantly higher level of ID1 gene than the intermediate prognosis group (Median: 6630, range: 66 - 1 840 798) (P = 0.006). The expression level of ID1 gene was positively associated with older age (age ≥ 60 years vs < 60 years, P = 0.002) and higher WBC count (WBC ≥ 10×10(9)/L vs < 10×10(9)/L, P = 0.005). Young patients (age < 60 years) who were not obtained the complete remission (non-CR) after the first cycle of chemotherapy harbored the high level of ID1 gene (Median: 9537 of non-CR vs 1268 of CR, P = 0.010).

CONCLUSIONSHigh expression level of ID1 gene was mostly seen in AML patients with adverse cytogenetics and older age (age ≥ 60 years), and may be associated with poor prognosis of AML. ID1 gene might be a prognostic molecular marker of AML.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Inhibitor of Differentiation Protein 1 ; genetics ; metabolism ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; metabolism ; Male ; Middle Aged ; Prognosis ; Young Adult

AIMTo study the effect of ligustrazine (LGT) and L-arginine(L-Arg)on function of mitochondria in myocardium after myocardial ischemia/reperfusion injury (MI/RI).

METHODS50 rabbits were randomly divided into five groups (n=10): Control group(A), MI/R group(B), MI/R + LGT group (C), MI/R+ L-Arg group (D), MI/R+ LGT + L-Arg group (E). The mitochondrial respiratory function, Ca2+ concentration ([Ca2+]m), malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were deter mined. Meanwhile, the contents of ATP and EC in the myocardial tissue were measured, respectively.

RESULTSIt was found that mitochondrial respiratory control rate (RCR), state 3 (ST3), SOD in C, D, E group were higher than those of B group, state 4 (ST4), [Ca2+]m, MDA were lower than those of B group, ATP and EC levels of myocardial tissue were higher than those in B group; and there were not significant differences between E and A group of above.

CONCLUSIONLGT and IL-Arg can improve function of mitochondria in myocardium after ischemia/reperfusion injury of myocardium in rabbits by decreasing oxygen free radical level and Ca" overload in the mitochondria.

Animals ; Arginine ; pharmacology ; Calcium ; metabolism ; Malondialdehyde ; analysis ; Mitochondria, Heart ; drug effects ; metabolism ; Myocardial Reperfusion Injury ; metabolism ; physiopathology ; Pyrazines ; pharmacology ; Rabbits ; Superoxide Dismutase ; metabolism

Adolescent ; Adult ; Aged ; B-Lymphocytes, Regulatory ; Case-Control Studies ; Female ; Humans ; Immunosuppression ; Male ; Middle Aged ; Thrombocytopenia ; blood ; immunology ; therapy ; Treatment Outcome ; Young Adult

OBJECTIVETo study the clinical characteristics, risk factors and therapeutic outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia (Ph(+)aALL).

METHODSThe clinical data of 117 newly diagnosed adults with Ph(+)ALL in our hospital between January 1995 and December 2009 were retrospectively analyzed. And their prognoses were followed up.

RESULTSThere were 117(16.1%) of 727 aALL patients diagnosed as Ph(+)aALL. Among the 117 cases, 64.1% patients were classified as pre-B immunophenotype and 31.3% as common B immunophenotype, 37.5% patients with co-expression of myeloid antigens (CD13 or CD33), and 98.4% patients with positive CD34. The complete remission (CR) rate after 1 or 2 cycles of induction chemotherapy was 62.2% in Ph(+)aALL group versus 82% in Ph(-)aALL group (P = 0.000). The median disease-free survival time of Ph(+) group was 6 months and the median survival time was 9 months. Sole karyotype abnormality subgroup t(9;22) accounted for 53% of all Ph(+)aALL patients and additional karyotype abnormality subgroup, t(9;22) plus other chromosome variation, accounted for 47%. Patients in sole karyotype abnormality subgroup had slightly lower CR rate (59.6% vs 62.5%, P = 0.768), longer median survival time (7 months vs 4 months, P = 0.158), and higher 3-year overall survival rate (27.3% vs 14.4%, P = 0.271). For the myeloid antigen co-expressed patients and the only lymphocytic antigen expressed ones, CR rate was 56.0% and 61.5% (P = 0.750), the median survival time was 5 months and 4 months (P = 0.182), and the 3-year overall survival rate was 16.0% and 15.0% (P = 0.354), respectively. In the imatinib plus combination chemotherapy treatment group, 81.3% patients achieved CR, compared with that of 58.3% in patients treated with only traditional combination chemotherapy (P = 0.083). The median survival time was 9.5 months and 6 months (P = 0.003) in these two subgroup, and 3-year overall survival rate was 52.2% and 10.3% (P = 0.029), respectively. For the patients receiving allo-HSCT after CR and that receiving traditional consolidation chemotherapy, the median survival time was 15 months and 6 months (P = 0.000), and the 3-year overall survival rate was 62.0% and 10.3% (P = 0.000), respectively. For the patients receiving imatinib as consolidation-maintenance treatment and that receiving allo-HSCT, the median survival time was 12 months and 15 months (P = 0.300), and the 3-year overall survival rate was 64.7% and 62% (P = 0.505), respectively.

CONCLUSIONOf all adult ALL patients, the Ph(+) subgroup accounted for about 16.1%, which have unfavorable prognosis such as lower CR rate and shorter survival duration under traditional chemotherapy. Neither additional chromosome abnormalities to t(9;22) nor co-expression of myeloid antigen had negative effect on CR rate and survival duration. Addition of imatinib to the therapy was beneficial to improve the CR rate and survival duration. Either receiving imatinib as consolidation-maintenance treatment or allo-HSCT after complete remission can improve long-term survival rate of Ph(+) adult ALL group significantly.

Adult ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Male ; Philadelphia Chromosome ; Piperazines ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; genetics ; Prognosis ; Pyrimidines ; therapeutic use ; Retrospective Studies

OBJECTIVETo investigate the cytogenetic features of acute myeloid leukemia (AML) with t(8;21).

METHODSThe clinical characteristics of 154 cases of acute myeloid leukemia with t(8;21) in our hospital were analyzed retrospectively. According to the chromosome karyotype, all cases were divided into three groups: the group without additional chromosome abnormality, the group with single sex chromosome loss and the group with additional chromosome abnormalities other than sex chromosome loss.

RESULTIn this study, according to FAB classification, there were 127 cases of M2 (82.5%), 15 of M5 (9.7%), 6 of M4 (3.9%), 4 of M1(2.6%) and 2 of M0(1.3%). Cytogenetically, 85 (55.2%) AML patients with t(8;21) had additional chromosome abnormalities. The most common abnormalities were sex chromosome loss, of which -Y was detected in 44.1% of the male karyotype and X in 27.9%. Beside that, there were 9 cases of 9q- (5.8%), 5 of +8(3.3%),3 of +4(2.0%) and 17 of other chromosome anomalies (11.4%). In the group of t(8;21) with additional chromosome abnormalities, 11 cases (35.5%) were non-M2 AML, higher than that in single t(8;21) group (17.4%)(P<0.05); however, there was no significant difference between the group of single t(8;21) and the group of t(8;21) with single sex chromosome loss(P>0.05).

CONCLUSIONt(8;21) translocation is usually accompanied by additional chromosome abnormalities, particularly in M2; while t(8;21) with additional chromosome abnormalities other than sex chromosome loss is more frequently observed in non-M2 AML.

Adolescent ; Adult ; Chromosome Aberrations ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; Leukemia, Myeloid, Acute ; classification ; genetics ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Translocation, Genetic ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of the HAA regimen (homoharringtonine, cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML).

METHODSThe efficacy and safety of 236 de novo AML patients who received the HAA regimen as induction chemotherapy were retrospectively analyzed. The complete remission (CR) rate was assayed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test.

RESULTSThe overall CR rate was 78.0%, and 65.7% of the patients attained CR in the first induction cycle. The early death rate was 4.7%. The median followup time was 41(1-161) months. The estimated 5-year OS and 5-year RFS rates were 44.9% and 45.5%, respectively. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 92.9%,78.6%and 41.7%, respectively. The 5-year OS of favorable and intermediate group were 61.1% and 45.1%, respectively. The 5- year RFS of favorable and intermediate group were 49.0% and 45.4%, respectively. The median survival time of unfavorable group was only 5 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection.

CONCLUSIONThe HAA regimen is associated with a higher rate of CR and longer survival time and its toxicity could be tolerated.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo ascertain the causation of a pregnant woman with undefined pneumonia reported from the People's Hospital of Tongling city in Anhui province on November 2005.

METHODSEpidemiological and clinical information of the case was collected from the keypersons close to the case and referring to the medical record. A medical observation was carried out on the close contacts of the case and sick or dead poultry. Tracheal aspirates being collected were tested by both RT-PCR and real-time PCR to detect viral nucleic acids of A/H5N1, and were inoculated into special pathogen free (SPF) embryonated hens' eggs.

RESULTSThe pregnant woman was found to have been contacted with the sick/dead poultry directly on the 4th day before onset of illness. All the 122 close contacts were healthy after a 10-day medical observation. The major clinical features of the case were viral pneumonia with rapidly developed leukopenia and lymphopenia. The progress to acute respiratory distress syndrome and multiple organ dysfunction syndromes was found at clinical presentation. HA and NA gene of A/H5N1 virus were positive. The 8 gene fragments of A/Anhui/1/2005 (H5N1) isolated from the tracheal aspirates had not carried genes from a human virus through reassortment, and the receptor-binding site of the hemagglutinin was polybasic cleavage site.

CONCLUSIONThis was the first documented case of H5N1 infection in pregnant woman. The immunotolerant state of pregnancy might have predisposed to the fatal outcome of the patient.

Adult ; China ; Fatal Outcome ; Female ; Humans ; Influenza A Virus, H5N1 Subtype ; genetics ; isolation & purification ; Influenza, Human ; complications ; pathology ; Multiple Organ Failure ; Pneumonia ; virology ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Respiratory Distress Syndrome, Adult ; Trachea ; virology