Plasma and Cell Lysate Proteins Associated With Treatment Outcome in Acute Myeloid Leukaemia

@#Introduction: Drug-resistance is a major hindrance to successful treatment of AML. Current predictive biomarkers are mainly genetic aberrations and insufficient in foretelling treatment outcome in all acute myeloid leukaemia (AML) due to its heterogeneous and aggressive nature. Proteins are stable and reliable. Secreted proteins in AML may have predictive or prognostic values for early intervention. Proteomic studies on AML are few and further investigations will benefit in selection of best markers. The aim of the study was to identify differentially expressed plasma proteins in AML with different treatment outcome. Methods: Two-dimensional electrophoresis (2-DE) technique was utilised to identify proteins differentially expressed in chemo-sensitive/chemo-resistant AML. Plasma and peripheral blood mononuclear cell (PBMC) lysate proteome analysis were performed on six chemo-resistant, four chemo-sensitive and six healthy controls and seven chemo-resistant, three chemo-sensitive and six healthy controls, respectively. Each experiment was conducted in duplicate or triplicate. Images were captured and protein spots detected by software. Differentially expressed protein spots were excised from gel and proteins were identified using LC/MS/MS. Proteins spots that were also detected in healthy controls were excluded. Results: Comparing mean % volume of each spot demonstrated significantly enhanced expression of apoliprotein-E (APO-E) and haptoglobin (HP) (p<0.05) in plasma and HNRNP H1 (p=0.049) in cell lysate of chemo-sensitive group. Serotransferrin (STF) from plasma and DNA-PK from cell lysate (p=0.01) were associated with chemo-resistance. Conclusion: This preliminary study identified several potential predictive biomarkers associated with chemo-resistance/chemo-sensitivity to treatment in AML. Further studies with a larger number of samples are required to validate the results.

Identification of an acute myeloid leukaemia associated noncoding somatic mutation at 3′ end of HOXA cluster

Noncoding somatic mutations have been demonstrated to play important role in tumourigenesis. Here we show that there exists an acute myeloid leukaemia associated noncoding somatic mutation at 3′ terminal of conserved HOXA cluster. The mutation was identified in the bone marrow blasts but not peripheral blood mononuclear cells or buccal cells of two M3 (acute promyelocytic leukaemia, APL) type patients from 45 acute myeloid leukaemia patients. The mutation also existed in a pair of twins one of them developed acute myeloid leukaemia M4 (acute myelomonocytic leukaemia) type. The mutation resides in about 2-kb downstream of HOXA1 gene where a functional retinoic acid response element is located and also bound by histone demethylase KDM3B. Reporter assay showed that the mutation results in the upregulation of transcriptional activity and unresponsiveness to retinoic acid receptor. To sum up, we identified a new acute myeloid leukaemia associated noncoding somatic mutation.

Selection of reference genes for quantitative studies in acute myeloid leukaemia

@#Introduction: Quantitative polymerase chain reaction (qPCR) is commonly used in the investigation of acute myeloid leukaemias (AML). Stable reference genes (RG) are essential for accurate and reliable reporting but no standard method for selection has been endorsed. Materials and Methods: We evaluated simple statistics and published model-based approaches. Multiplex-qPCR was conducted to determine the expression of 24 candidate RG in AMLs (N=9). Singleplex-qPCR was carried out on selected RG (SRP14, B2M and ATP5B) and genes of interest in AML (N=15) and healthy controls, HC (N=12). Results: RG expression levels in AML samples were highly variable and coefficient of variance (CV) ranged from 0.37% to 10.17%. Analysis using GeNorm and Normfinder listed different orders of most stable genes but the top seven (ACTB, UBE2D2, B2M, NF45, RPL37A, GK, QARS) were the same. In singleplex-qPCR, SRP14 maintained the lowest CV in AML samples. B2M, one of most stable reference genes in AML, was expressed near significantly different in AML and HC. GeNorm selected ATP5B+SRP14 while Normfinder chose SRP14+B2M as the best two RG in combination. The median expressions of combined RG genes in AML compared to HC were less significantly different than individually implying smaller expression variation after combination. Genes of interest normalised with RG in combination or individually, displayed significantly different expression patterns. Conclusions: The selection of best reference gene in qPCR must consider all sample sets. Model-based approaches are important in large candidate gene analysis. This study showed combination of RG SRP14+B2M was the most suitable normalisation factor for qPCR analysis of AML and healthy individuals.

Microarray-Based Genomic Analysis Identifies Germline and Somatic Copy Number Variants and Loss of Heterozygosity in Acute Myeloid Leukaemia

@#Introduction: Insights into molecular karyotyping using comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays enable the identification of copy number variations (CNVs) at a higher resolution and facilitate the detection of copy neutral loss of heterozygosity (CN-LOH) otherwise undetectable by conventional cytogenetics. The applicability of a customised CGH+SNP 180K DNA microarray in the diagnostic evaluation of Acute Myeloid Leukaemia (AML) in comparison with conventional karyotyping was assessed in this study. Methods: Paired tumour and germline post induction (remission sample obtained from the same patient after induction) DNA were used to delineate germline variants in 41 AML samples and compared with the karyotype findings. Results: After comparing the tumour versus germline DNA, a total of 55 imbalances (n 5-10 MB = 21, n 10-20 MB = 8 and n >20 MB = 26) were identified. Gains were most common in chromosome 4 (26.7%) whereas losses were most frequent in chromosome 7 (28.6%) and X (25.0%). CN-LOH was mostly seen in chromosome 4 (75.0%). Comparison between array CGH+SNP and karyotyping revealed 20 cases were in excellent agreement and 13 cases did not concord whereas in 15 cases finding could not be confirmed as no karyotypes available. Conclusion: The use of a combined array CGH+SNP in this study enabled the detection of somatic and germline CNVs and CN-LOHs in AML. Array CGH+SNP accurately determined chromosomal breakpoints compared to conventional cytogenetics in relation to presence of CNVs and CN-LOHs.

Unexpected infant death secondary to a pulmonary infiltration due to acute myelocytic leukaemia

Acute myeloid leukaemia (AML) often presents with non-specific symptoms such as fatigue, anaemia or infection. Pulmonary involvement is uncommon in AML during the course of the disease and is usually caused by infection, haemorrhage, leukaemic pulmonary infiltrates and leukostasis. Lung localization of AML is very uncommon and potentially life threatening if not diagnosed and treated rapidly. The authors describe the sudden death of an asymptomatic five-month-infant because of a misdiagnosed lung localization of AML. Autopsy examination followed by histopathological studies showed an extensive leukostasis and extramedullary leukaemic infiltrating the lungs. Special stains and immunohistochemical studies revealed findings consistent with acute myelogenous leukaemia. This case suggests that underlying acute leukaemia should be considered as a cause of flu-like symptoms in infants. Medical personnel are urged to be alert to fever, sore throat, weakness and dyspnea that may be characteristic of serious systemic diseases.

High fms-like tyrosine kinase-3 (FLT3) receptor surface expression predicts poor outcome in FLT3 internal tandem duplication (ITD) negative patients in adult acute myeloid leukaemia: a prospective pilot study from India.

Background & objectives: Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcome in patients with acute myeloid leukaemia (AML). Data for FLT3 surface expression in relation to FLT3 internal tandem duplication (ITD) status and outcome are not available from India. The objective of the current study was to investigate adult patients with AML for FLT3 expression and FLT3 ITD mutation, and their association with long-term outcome. Methods: Total 51 consecutive de novo AML patients aged 18-60 yr were enrolled in the study. FLT3 ITD was detected by polymerase chain reaction (PCR); flowcytometry and qPCR (Taqman probe chemistry) were used for assessment of FLT3 protein and transcript, respectively. Kaplan Meier curves were obtained for survival analysis followed by log rank test. Results: FLT3 ITD was present in eight (16%) patients. Complete remission was achieved in 33 (64.6%) patients. At 57.3 months, event free survival (EFS) was 26.9±6.3 per cent, disease free survival (DFS) 52.0±9.2 per cent, and overall survival event (OS) 34.5±7.4 per cent. FLT3 surface expression was positive (>20%) by flow-cytometry in 38 (88%) of the 51 patients. FLT3 surface expression and transcripts were not associated with FLT3 ITD status. FLT3 expression was significantly associated with inferior EFS (P=0.026) and OS (P=0.018) in those who were negative for FLT3 ITD. Interpretation & conclusions: This study evaluated FLT3 ITD mutation along with FLT3 expression in AML patients, and associated with survival. Negative impact of FLT3 surface expression on survival was observed in AML patients who were FLT3 ITD negative.

Dismal outcome of therapy-related myeloid neoplasm associated with complex aberrant karyotypes and monosomal karyotype: a case report

Introduction: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival. Case report: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis. Discussion and Conclusion: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.

Cohorte de supervivencia en pacientes menores de 60 años con leucemia mieloide aguda de acuerdo con la citogenética y el tratamiento de consolidación / Survival cohort of patients under 60 years with acute myeloid leukemia according to cytogenetics and consolidation treatment / Coorte de sobrevivência em pacientes menores de 60 anos com leucemia mielóide aguda de acordo com a citogenética e o tratamento de consolidação

Introducción: la supervivencia de pacientes con leucemia mieloide aguda (LMA) puede variar de acuerdo con el cariotipo y el tratamiento recibido. Métodos: en esta cohorte retrospectiva se evaluaron la supervivencia, sus factores pronósticos y su asociación con el cariotipo inicial, en 66 pacientes con LMA menores de 60 años, que recibieron quimioterapia o trasplante alogénico de médula ósea. Resultados: la supervivencia global a 2 años fue del 90 % para el grupo de bajo riesgo, del 61 % para el de riesgo intermedio y del 30 % para el de riesgo alto (p = 0,016). Se hallaron como factores que afectan la supervivencia global el no haber alcanzado la remisión completa (HR: 16,36; IC 95 %: 6,17-43,33) y el no recibir trasplante de progenitores hematopoyéticos (HR: 4,76; IC 95 %: 1,36-16,69). Como factores de riesgo para la recaída de la enfermedad se identificaron el cariotipo de alto riesgo (HR: 9,18; IC 95 %: 1,22- 68,56) y la no realización de trasplante (HR: 3,06; IC 95 %: 1,14-8,18). Conclusión: este estudio sugiere que en Colombia la supervivencia global de los pacientes con LMA con riesgo citogenético intermedio o alto puede mejorar cuando reciben como parte del tratamiento el trasplante de progenitores hematopoyéticos.

Introduction: Survival of patients with acute myeloid leukemia (AML) differs according to karyotype and the treatment they receive. Methods: In this retrospective cohort we evaluated survival, its prognostic factors and its association with the initial karyotype in 66 patients younger than 60 years with AML, who received chemotherapy or allogeneic bone marrow transplantation. Results: Overall survival at 2 years was 90 % in the low risk group, 61 % in the intermediate risk group and 30 % in the high risk group (p = 0.016). The following factors affected overall survival: not having reached complete remission (HR: 16.36; IC 95 %: 6.17-43.33), and not having received haematopoietic stem cell transplantation (HR: 4.76; IC 95 %: 1.36-16.69). As risk factor for relapse we found: High risk karyotype (HR: 9.18; IC 95 %: 1.22- 68.56) and not having performed haematopoietic stem cell transplantation (HR: 3.06; IC 95 %: 1.14-8.18). Conclusion: This study suggests that in Colombia the global survival of young patients with AML with intermediate or high cytogenetic risk at diagnosis may improve when they receive hematopoietic stem cell transplantation as part of the treatment.

Introdução: a sobrevivência de pacientes com leucemia mielóide aguda (LMA) pode variar de acordo com o cariótipo e o tratamento recebido Métodos: nesta coorte retrospectiva se avaliaram a sobrevivência, seus fatores prognósticos e sua associação com o cariótipo inicial, em 66 pacientes com LMA menores de 60 anos, que receberam quimioterapia ou transplante alogênico de medula óssea. Resultados: a sobrevivência global a 2 anos foi do 90 % para o grupo de baixo risco, do 61 % para o de risco intermédio e do 30 % para o de risco alto (p = 0,016). Acharam-se como fatores que afetam a sobrevivência global o não ter atingido a remessa completa (HR: 16,36; IC 95 %: 6,17-43,33) e o não receber transplante de progenitores hematopoiéticos (HR: 4,76; IC 95 %: 1,36-16,69). Como fatores de risco para a recaída da doença se identificaram o cariótipo de alto risco (HR: 9,18; IC 95 %: 1,22- 68,56) e a não realização de transplante (HR: 3,06; IC 95 %: 1,14-8,18). Conclusão: este estudo sugere que na Colômbia a sobrevivência global dos pacientes com LMA com risco citogenético intermédio ou alto pode melhorar quando recebem como parte do tratamento o transplante de progenitores hematopoiéticos.

A Case Report of Concurrent IDH1 and NPM1 Mutations in a Novel t(X;2)(q28;p22) Translocation in Acute Myeloid Leukaemia without Maturation (AML-M1)

Acute myeloid leukaemia (AML) is one of the fatal haematological malignancies as a consequence of its genetic heterogeneity. At present, the prediction of the clinical response to treatment for AML is based not only on detection of cytogenetic aberrations but also by analysing certain molecular genetic alterations. There are limited in sights into the contribution, disease progression, treatment outcome, and characterisation with respect to the uncommon chromosomal abnormalities leading to AML. Here, we describe the clinical, morphological, cytogenetic, and mutational findings of a 52-year-old female patient with AML without maturation (AML-M1). Conventional karyotyping and spectral karyotyping (SKY) were done on metaphase chromosomes from bone marrow cells at the time of diagnosis. A mutation analysis was performed on the hotspot regions of various genes, including FLT3, CEBPA, NPM1, RAS, c-KIT, IDH1 and IDH2. Cytogenetic and mutation analyses revealed a novel translocation, t(X;2)(q28;p22), with both NPM1 and IDH1 mutations. To the best of our knowledge, the presence of both NPM1 and IDH1 mutations in t(X;2) (q28;p22) is a novel finding in AML.

Sarcoma granulocítico en una paciente con leucemia mieloide crónica / Granulocytic sarcoma in a female patient with chronic myeloid leukemia

El sarcoma granulocítico es un tumor localizado poco común, compuesto de células granulocíticas inmaduras. Generalmente se presenta en pacientes con leucemia mieloide aguda, síndromes mielodisplásicos o leucemia mieloide crónica. Puede ocurrir en cualquier localización anatómica. Reportamos el caso de una mujer de 41 años con el diagnóstico de leucemia mieloide crónica que presentó edema en brazo derecho que no remitía a pesar de tratamiento antibiótico y fasciotomía. El estudio histológico de la biopsia la lesión tomada mostró un sarcoma granulocítico. En este trabajo se revisa la citogenética, presentación clínica, diagnóstico y pronóstico de este síndrome tumoral.

Granulocytic sarcoma is an uncommon and localized extramedullary tumor composed of immature granulocytic cells. It may present in patiens with acute myeloid leukaemia, myelodysplastic syndrome or chronic myelogenous leukaemia. It may occur in any anatomical site. We report on the case of a 41 year old female diagnosed with chronic myelogenous leukaemia who presented with right arm swelling that did not resolve after antibiotic and surgical fasciotomy. The histological examination showed granulocytic sarcoma. In this report the citogenetics, clinical presentation, diagnosis and outcome of granulocytic sarcoma was reviewed.

Haematological & molecular profile of acute myelogenous leukaemia in India.

Background & objectives: Recurrent balanced translocations are generally recognized to be a major parameter for prognostication in acute myeloid leukaemia (AML). The chromosomal translocation t(15;17) results in PML/RARα fusion gene, t(8;21) results in AML1/ETO fusion gene and Inv 16 generates CBFβ/MYH11 fusion gene. Patients with these mutations have a good prognosis unlike abnormalities in chromosome 5 or 7 or FLT3 genes. Therefore, we screened the AmL patients for known specific genetic abnormalities that could lead to more definitive prognoses. Methods: A total of 113 AML patients were evaluated at diagnosis based on routine morphology and cytochemistry and classified according to the WHO criteria. The distribution of AML subtypes was M1(1), M2(32), M3(57), M4(14), M5(1), M6(1) and seven cases where morphological subtype could not be classified. RT-PCR was performed to identify PML/RARα, AML1/ETO, CBFβ/MYH11 and FLT3 internal tandem duplication (ITD). Results: Of the 57 patients with M3 subtype, 55 had the PML-RARα fusion transcript. The prevalence of bcr3 (short isoform) was higher (62%) than that of bcr1 (long isoform) (38%) and no correlation was found with age, sex or white blood cell count. FLT3 internal tandem duplication (ITD) mutations were more frequent in patients with APL than in other AML subtypes (17.5 vs. 8.9%), the frequency greater in patients with bcr3 isoform (70%) than in those with in bcr1 isoform (30%). Patients with FLT3/ITD mutations had a significantly higher median white cell count than those without these mutations (55 x 109/l vs. 6.3 x 109/l; P<0.001). More patients with FLT3/ITD mutations died early (53%) than those without these mutations (16%) (P<0.01). AML1-ETO fusion transcript was detected in 16 of 56 patients with no correlation with clinical or haematological parameters. Interpretation & conclusion: The results of the present study showed presence of bcr3 (short isoform) higher than bcr1 (long isoform). FLT3 internal tandem duplication (ITD) mutation was predominant in acute promyelocytic leukaemia patients with bcr3 isoform. Thus, patients with APL who have FLT3 mutation appear to have a poorer prognosis. Therefore, rapid identification of specific translocations at diagnosis is important for prognostic purposes and their detection should be incorporated into routine assessment.

The role of hematopoietic stem cell transplantation in the elderly patient with acute myeloid leukaemia / O papel do transplante de célula-tronco hematopoiética em pacientes idosos com leucemia mielóide aguda

Older adults with Acute Myeloid Leukaemia (AML), when compared to younger patients with the same disease, have a poor prognosis and represent a discrete population in terms of disease biology, treatment-related complications, and overall outcome. As a result, older patients require distinctive management approaches. For 85 percent-95 percent of older AML patients, any therapy ultimately will be purely palliative. No randomized trial has ever demonstrated that any amount of post-remission therapy in older AML patients provides better outcomes than no post-remission therapy. The only studies demonstrating that long-term Disease Free Survival (DFS) is possible in older AML patients have included remission induction and post-remission therapy. For these reasons alternative post-remission strategies, including autologous or allogeneic transplantation have been explored also in people over sixty considered fit for aggressive therapy. Up to now the data available from clinical trials suggest that the stem cell transplant procedure is promising, and can lead to long-term survival, but it is feasible only in a minority of fit elderly patients. The main limits of Autologous Stem Cell Transplantation (ASCT) are represented by the low percentage of patients able to mobilize a sufficient amount of stem cells and by the still high relapse incidence after ASCT, especially in those with poor prognostic factors; for these patients the allogeneic transplant procedure, by using non myeloablative conditioning regimens, could offer a better chance of cure, thanks to the Graft versus Leukemia (GVL) effect, but there are no prospective trials showing the superiority of any transplant approach over conventional treatment in this subset of patients.

Pacientes idosos com leucemia mielóide aguda (LMA), quando comparados com pacientes jovens com a mesma doença, apresentam prognóstico pobre e representam uma população particular em termos biológicos, complicações relacionadas ao tratamento e evolução clínica. Como resultado de tudo isto, o paciente idoso requer manuseio distinto. Para 85 por cento-95 por cento dos pacientes idosos a abordagem terapêutica será finalmente apenas paliativa. Nenhum estudo randomizado demonstrou qualquer vantagem de qualquer terapêutica na fase pós-remissão. Os únicos estudos que mostraram alguma vantagem em termos de sobrevida livre de doença em pacientes idosos portadores de LMA incluíram juntas as fases de indução e consolidação da remissão. Por estas razões, estratégias terapêuticas alternativas pós-remissão, incluindo transplante autólogo ou alogênico, têm sido exploradoras também em pacientes acima de 60 anos com boa performance status para as terapias de alta dose. Até agora, os dados disponíveis dos estudos clínicos sugerem que o procedimento usando célula-tronco é promissor e pode levar a sobrevida de longo prazo, porém factível apenas em uma minoria de pacientes idosos. Os principais limites para o transplante autólogo são representados pela baixa porcentagem de pacientes capazes de mobilizar suficiente quantidade de células-tronco e pela, ainda, alta incidência de recidiva após o transplante, principalmente em pacientes de fatores de mau prognóstico. Para o transplante alogênico, o uso de regimes de intensidade reduzida pode oferecer uma melhor oportunidade de cura graças ao efeito enxerto versus leucemia. Porém, não existem estudos clínicos comprovando a superioridade de qualquer modalidade de transplante em relação à terapia convencional.

Generation and Qualification of Functionally Active Leukemia-derived DCs from Malignant Blasts in Acute Leukemia / 대한혈액학회지

BACKGROUND: Dendritic cells (DCs) are increasingly being utilized for anti-cancer immunotherapy. Acute myeloid leukemia (AML) blasts are able to generate leukemia-derived DC. Advances in culture techniques and AML-DC characterization justify possible clinical applications. We investigated the ability of AML, acute lymphoblastic leukemia (ALL) and biphenotypic acute leukemia (BAL) blasts to differentiate into DCs in vitro and the qualified function of the leukemia-derived DCs. METHODS: Leukemia cells from 11 patients with AML, 3 patients with ALL and 2 patients with BAL were cultured with GM-CSF, IL-4 and with or without SCF. Cultured leukemia cells were evaluated by phenotype, mixed lymphocyte reaction (MLR), cytokine production and cytotoxic T cell (CTL) inducing activity. RESULTS: DCs were generated with GM-CSF and IL-4 from the leukemic blasts in 72% of the AML patient cells. MHC class I/II, CD11c and ICAM-1 were highly expressed in the AML-derived DCs. MLR and enzyme linked immunospot (ELISPOT) assays demonstrated that AML-DCs were able to induce T cell proliferation and activation into IFN-gamma secreting effector cells. The ALL blasts from two out of three patients differentiated into DCs with MHC class I/II+, CD11c+ only in the presence of GM-CSF, SCF and IL-4 for 14 days. CONCLUSION: These results suggest that functionallyactive DCs can be differentiated from AML blasts using GM-GSF and IL-4 and ALL, BAL blasts were differentiated into DCs only under stem cell-DC culture conditions.

Effect of 8-nitrochyrsin on the proliferation and apoptosis of HL-60 cells / 基础医学与临床

Objective To investigate the effect of 8-Nitrochyrsin on cell proliferation and cell apoptosis of HL-60 cells in vitro.Methods 8-Nitrochyrsin on proliferation of HL-60 cells was detected by MTT assay;The trypan blue exclusion method was used to count the number of viable and dead cells,then the survival rate and growth curve were achieved;DNA ladder bands were observed by DNA agarose gel electrophoresis;HL-60 cell apoptotic percentage was detected by flow cytometry with PI staining.Results 8-Nitrochrysin inhibited proliferation of HL-60 cells in a concentration-dependent manner;8-Nitrochyrsin possess the inhibitory effect on the proliferation and growth of HL-60 cells;8-Nitrochrysin possess the significantly effect of inducing apoptosis of HL-60 cells.Conclusion 8-Nitrochyrsin possess the inhibitory effect of the proliferation and growth of HL-60 cells and significantly induces apoptosis of HL-60 cells.