Numerous genetic abnormalities which can not be identified by cytogenetic detection (e.g., gene mutations, gene expression abnormalities) have been gradually found, which means that the further molecular classification of AML (acute myeloid leukemia) with distinctive prognosis have arrived. For example, mutations of the transcription factor (CCAAT enhancer binding factor alpha, C/EBPalpha) or nucleophosmin-1 (NPM1) may predict better prognosis, whereas partial tandem duplications of the MLL gene (MLL-PTD), internal tandem duplications of FLT3 (FLT3-ITD) or mutations of WT1 gene confer worse prognosis. This review focuses on the features and relationship of these genetic abnormalities, as well as their influence on the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Prognosis

Acute myeloid leukemia (AML) is a rare type of childhood acute leukemia, which has a worse prognosis than childhood acute lymphoblastic leukemia. Over the past decade, significant progress has been made in the treatment of childhood AML and the 5-year event-free survival rate may be as high as 70% in developed countries. This survival improvement is largely attributable to risk-stratified treatments, therapies tailored to individual patients based on the biological characteristics of the disease, and continuously improving supportive care. An accurate diagnosis is the prerequisite for risk stratification, prognostic evaluation and therapeutic decision making. How to reduce early mortality and thus improve overall survival, how to implement appropriate supportive treatment to reduce treatment-associated complications, and how to reduce treatment-related mortality are the key to the improvement of therapies for childhood acute myeloid leukemia.
Child ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; mortality ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics

Acute myeloid leukemia (AML) is a group of diseases with a conspicuous heterogeneity. Following the development of cytogenetics, multiple reproducible chromosome aberrations have been discovered in AML, many of which not only are diagnostic markers for specific AML subtypes but also significant prognostic factors for determining complete remission (CR), relapse risk, and overall survival (OS). However, with the foundation of available chromosome analysis, a large group of acute myeloid leukemia (AML) patients, 40% to 49% of adults and 25% of children had not been found abnormality of chromosome karyotype under microscope. These so-called cytogenetically normal acute myeloid leukemia (CN-AML) patients have usually been classified in an intermediate-risk prognostic category. Nevertheless, the outcome of the CN-AML patients are varied in clinical studies, likely because there exist diverse gene mutations in these patients according to recent researches. Those mutations at the molecular level, on basis of which AML could be further classified, are significantly associated with CN-AML patients and offer potential targets for specific therapeutic studies. The review focuses on research advances abroad in this field including gene mutations suggesting bad prognosis such as FMS-related tyrosine kinase 3 gene mutation, Baalc gene and ETS-related gene hyperexpression, Wilms' tumor gene mutation and other gene mutations as well as gene mutations suggesting good prognosis such as nucleophosmin gene mutation, mixed lineage leukemia-partial tandem duplication, CCAAT/enhancer-binding protein α gene mutation.
Cytogenetics ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Prognosis

MRD detection in children leukemia has a potential importance to predict clinical outcome and to modify treatment protocols of the diseases. Although some patients with leukemia have achieved complete remission according to the clinical and morphological criteria, there are still very low numbers of malignant cells that can not be discriminated by morphology and remained in bone marrow, which is called minimal residual disease (MRD) and is the main reason leading to relapse. MRD detection has an important significance for designing treatment protocols. Several methods of MRD detection have been developed. These include conventional cytogenetics, fluorescence in situ hybridization (FISH), flow-cytometric immunophenotyping (FCM), Southern blot and polymerase chain reaction (PCR) techniques, etc. Each of these techniques has its advantages and disadvantages, so not all of them are suitable for clinical MRD detection because of several inherent disadvantages, such as limited sensitivity, time-consuming, high cost, or requiring high-quality DNA or RNA. For example, the sensitivities of conventional cytogenetics, FISH, FCM and Southern blot approaches for MRD monitoring are 10(-1) - 10(-2), 10(-2), 10(-3) - 10(-4) and 10(-1), respectively. Relatively, PCR can reach a good sensitivity of 10(-4) - 10(-6), and show more advantages, such as fast, specific, simple and low-cost, as well as minimal amounts of DNA or RNA for detection, etc., so PCR has its specific features for MRD detection. In this review, the progress on the detection technique for screening leukemia specific marker by muitiplex PCR and FQ-PCR in recent years are summarized.
Child ; Humans ; Leukemia ; diagnosis ; genetics ; Neoplasm, Residual ; diagnosis ; genetics ; Polymerase Chain Reaction ; methods ; Sensitivity and Specificity

The Philadelphia chromosome was the first genetic abnormality discovered in cancer (in 1960), and it was found to be consistently associated with CML. The description of the Philadelphia chromosome ushered in a new era in the field of cancer cytogenetics. Accumulating genetic data have been shown to be intimately associated with the diagnosis and prognosis of neoplasms; thus, karyotyping is now considered a mandatory investigation for all newly diagnosed leukemias. The development of FISH in the 1980s overcame many of the drawbacks of assessing the genetic alterations in cancer cells by karyotyping. Karyotyping of cancer cells remains the gold standard since it provides a global analysis of the abnormalities in the entire genome of a single cell. However, subsequent methodological advances in molecular cytogenetics based on the principle of FISH that were initiated in the early 1990s have greatly enhanced the efficiency and accuracy of karyotype analysis by marrying conventional cytogenetics with molecular technologies. In this review, the development, current utilization, and technical pitfalls of both the conventional and molecular cytogenetics approaches used for cancer diagnosis over the past five decades will be discussed.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia/diagnosis/genetics/pathology ; Neoplasms/*diagnosis/genetics/pathology ; Prognosis

Acute Disease ; Antigens, CD ; analysis ; Biomarkers, Tumor ; analysis ; Chromosome Aberrations ; Diagnosis, Differential ; Humans ; Immunophenotyping ; Leukemia ; classification ; diagnosis ; genetics ; immunology ; Leukemia, Biphenotypic, Acute ; classification ; diagnosis ; genetics ; immunology ; Phenotype

The P53 gene has the important functions including induction of apoptosis, regulation of cell cycle, repair of DNA damage. The mutation of the P53 gene exists in more than 50% of human tumors and 13% of hematological malignancies. The P53 gene abnormality is closely related with the clinical course and prognosis of leukemia. The P73 or P63 gene, the member of the P53 family not only possesses similar to P53 activity of inducing apoptosis, activating transcription, but also plays different biological effects according to protein structural diversity, and even antagonises the function of the P53 gene. Researchers found that P73 or P63 gene also has the dual characteristics of the tumor suppressor and oncogene, and shows different expression and function in different types, different stages of leukemia. In this article, P53 family (P53, P73, P63) gene structure, biological function and the relationship of the three genes with the course, prognostic outcome, treatment and other clinical features of the leukemia are reviewed.
Gene Expression Regulation, Neoplastic ; Genes, p53 ; Humans ; Leukemia ; diagnosis ; genetics ; pathology ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo evaluate the effects of DNMT3A gene mutation on prognosis of patients with acute myeloid leukemia (AML) by a meta-analysis.

METHODSMethods of Cochrane systematic review was followed by 7 databases,including PubMed, Embase, Ovid, CNKI, CBM, WanFang Data and VIP, were searched for peer-reviewed articles related to DNMT3A gene mutations and prognosis of patients with AML.Then manual retrieval was applied into literature references. After the evaluation of quality and extract of clinical trialliterature data, Stata 11.0 was employed to perform meta-analysis.

RESULTSSeven randomized controlled trials involving 1493 cases were included in the meta-analysis. The prognosis of patients with DNMT3A mutations and without DNMT3A mutations was compared. There was no statistically significant difference in complete remission(CR) rate (OR=1.034, 95%CI: 0.596~1.796, P=0.905 between two groups, but the overall survival (OS（HR=1.990, 95%CI: 1.463~2.510, P=0.000 and disease free survival (DFS) (HR= 2.840, 95%CI: 1.063~4.613, P=0.002) of patients without DNMT3A mutations were longer than those with DNMT3A mutation.

CONCLUSIONDNMT3A gene mutation is an independent risk factor of poor prognosis of patients with acute myeloid leukemia.

DNA (Cytosine-5-)-Methyltransferases ; genetics ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Mutation ; Prognosis ; Risk Factors

OBJECTIVETo review the implications for diagnosis, pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia (CNL).

DATA SOURCESData cited in this review were obtained mainly from PubMed and Medline from 1993 to 2013 and highly regarded older publications were also included. The terms "chronic neutrophilic leukemia" and "diagnosis" were used for the literature search.

STUDY SELECTIONWe identified, retrieved and reviewed the information on the clinical and laboratory features, the new genetic findings, prognosis and disease evolution and management of CNL.

RESULTSThe discovery of high-frequency granulocyte-colony stimulating factor receptor (CSF3R) mutations in CNL identifies a new major diagnostic criterion, and lends more specificity to the World Health Organization (WHO) diagnostic criteria for CNL, which are variably applied in routine clinical practice.

CONCLUSIONSIn patients for whom the cause of neutrophilia is not easily discerned, the incorporation of CSF3R mutation testing can be a useful point-of-care diagnostic to evaluate the presence of a clonal myeloid disorder, as well as providing the potential for genetically informed therapy. The oncogenic CSF3R mutations are molecular markers of sensitivity to inhibitors of the SRC family-TNK2 and JAK kinases and may provide a new avenue for therapy.

Carrier Proteins ; genetics ; Female ; Humans ; Leukemia, Neutrophilic, Chronic ; diagnosis ; genetics ; Male ; Mutation ; Nuclear Proteins ; genetics ; Receptors, Colony-Stimulating Factor ; genetics

The study was purposed to investigate the significance of id4 gene promoter methylation in monitoring AML patients with complete remission (CR). Methylation specific-PCR (MS-PCR) were used to detect the status of promoter methylation of id4 gene in bone marrow samples from AML patients with CR who had accepted induction with DA or IA and 4 to 5 consolidation chemotherapy with Ara-C. The results showed that in the all 32 patients, 15 were found to show id4 promoter methylation and 7 out of the 15 were found relapsed or tendency to relapse in the following-up period. While all the 17 patients with id4 unmethylation were still in their CR status in the same period. In conclusion, id4 promoter methylation might be a predictor for relapse of AML patients with CR in certain degree.
DNA Methylation ; Humans ; Inhibitor of Differentiation Proteins ; genetics ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Neoplasm, Residual ; diagnosis ; genetics ; Promoter Regions, Genetic ; genetics