Microvesicles (MVs) are the heterogeneous mixtures of vesicles. MVs released by leukemia cells constitute an important part of the leukemia microenvironment. MVs might act as important reservoirs of microRNAs (miRNAs). It is worth evaluating whether MVs possess some unique miRNA contents that are valuable in understanding the pathogenesis. In this study, we investigated the miRNA expression patterns of Nalm-6-derived MVs, Jurkat-derived MVs and normal cell-derived MVs using miRNA microarrays. The potential target genes regulated by differentially expressed miRNAs were also predicted and analyzed. Results demonstrated that 182 miRNAs and 166 miRNAs were differentially expressed in Nalm-6-MVs and Jurkat-MVs, respectively. Many oncogenes, tumor suppressors and signal pathway genes were targeted by these aberrantly expressed miRNAs, which might contribute to the development of B-ALL or T-ALL. Our findings expanded the potential diagnostic markers of ALL and provided useful information for ALL pathogenesis.
Gene Expression Profiling ; Gene Expression Regulation, Leukemic ; Humans ; Jurkat Cells ; MicroRNAs ; genetics ; Multivesicular Bodies ; genetics ; Oligonucleotide Array Sequence Analysis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; pathology ; Reverse Transcriptase Polymerase Chain Reaction

<b>OBJECTIVEb>To analyze the incidence, clinical characteristics and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL).

<b>METHODSb>From January 1999 to April 2005, 305 patients with newly diagnosed ALL were enrolled in protocol ALL-XH-99. The clinical characteristics of these children were analysed.

<b>RESULTSb>Of 305 childhood ALL patients, 43 were T-ALL. There were 34 males among the 43 T-ALLs. The mean age at diagnosis was 7.8 (2.2 to 16.4) years, 29 (67.4%) cases of them were older than 10 years, and 27 (62.8%) cases had initial WBC count more than 50 x 10(9)/L. In comparison with that of B cell ALL (B-ALL), the percentages of age older than 10 years, initial WBC count more than 50 x 10(9)/ L, prednisone poor response (PPR), and failed to achieve remission at day 19 of induction chemotherapy in the T-ALLs were all higher. No statistic difference was found in sex between them. The eight-year event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS) were (40.2 +/- 10.1)%, (51.4 +/- 11.6)% and (49.8 +/- 9.9)% for T-ALL, and (72.1-3.0)%, (83.2 +/- 2.7)%, and (76.6 +/- 2.9)% for B-ALL, respectively, being differed significantly between the two types of ALL (P < 0.01).

<b>CONCLUSIONb>There were statistic differences between T-cell and B-cell childhood ALLs in age, initial WBC count, early response to therapy, and eight-year EFS and RFS. Childhood T-ALL was associated with a worse prognosis than other sub-types of childhood ALL.

Adolescent ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Humans ; Immunophenotyping ; Infant ; Karyotyping ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; pathology ; therapy ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; pathology ; therapy ; Prognosis

CD4 Antigens ; metabolism ; CD56 Antigen ; metabolism ; Dendritic Cells ; pathology ; Diagnosis, Differential ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Hematologic Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Leukemia, Myeloid ; pathology ; Lymphoma, Extranodal NK-T-Cell ; pathology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Skin Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery

Burkitt Lymphoma ; metabolism ; pathology ; Cell Nucleus ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Lymphoma, B-Cell ; classification ; metabolism ; pathology ; Lymphoma, Follicular ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Mantle-Cell ; metabolism ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; SOXC Transcription Factors ; genetics ; metabolism

<b>OBJECTIVEb>To report on a rare case of B-lineage acute lymphoblastic leukemia (B-ALL) with t(14;14) (q11;q32) and clarify its clinical and molecular cytogenetic features.

<b>METHODSb>Clinical data of a B-ALL patient with t(14;14) (q11;q32) were analyzed. After 24 hour of unstimulated culturing, chromosome specimens of bone marrow cells were prepared with regular method, and R-banding was used for karyotype analysis. Fluorescence in situ hybridization (FISH) analysis was performed on fixed bone marrow cells using IGH dual-color break-apart probe, CEBPE dual-color break-apart probe, whole chromosome paint (WCP) probe for chromosome 4, and Chromoprobe Multiprobe-ALL System probe.

<b>RESULTSb>The 39-year-old female was diagnosed with B-ALL based on morphologic and immunophenotypic analyses. Conventional cytogenetic analysis showed a karyotype of 47, XX, +4, t(14;14) (q11;q32) [20], which was confirmed by FISH analysis. FISH using IGH-dual-color break-apart probe confirmed involvement of IGH gene in t(14;14) (q11;q32), and FISH using CEBPE dual-color break-apart probe indicated that CEBPE is the partner gene involved in t(14;14) (q11; q32). The patient achieved complete remission (CR) after a round of combined chemotherapy. At the time of follow-up, she had remained CR for more than 6 months.

<b>CONCLUSIONb>t(14;14) (q11;q32) simultaneously involving IGH and CEBPE genes in B-ALL is a rare but recurrent genetic abnormality that may identify a new subgroup of B-ALL. In B-ALL patients, t(14; 14) (q11; q32) involving IGH/CEBPE translocation may indicate a better prognosis.

Adult ; Chromosomes, Human, Pair 14 ; Cytogenetics ; methods ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Humans ; Karyotype ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; pathology

To evaluate the expression of cytoplasmic CD79a (CyCD79a) and other commonly used B-lymphoid immunomarkers including cytoplasmic CD22 (CyCD22), CD19, CD20 and CD10 in various acute leukemia cells and to define the most sensitive and specific markers in the diagnosis of precursor B-cell acute lymphoblastic leukemia (pB-ALL), the immunophenotypic data from 221 de novo adult and pediatric acute leukemia patients as studied using multi-parameter flow cytometry in addition to routine morphologic and enzyme cytochemical assay, were retrospectively analyzed. Cytogenetic and/or molecular biological data in all 45 cases of acute promyelocytic leukemia (APL) and 13 cases of acute leukemia suspected as AML with the fusion genes such as AML1/ETO and CBFbeta/MYH11 were investigated. The results showed that CyCD79a and CyCD22 were the most sensitive and specific markers respectively for pB-ALL. Expression of CyCD79a was seen in 100% of 58 cases of pB-ALL. At the same time, none (0%) of all 147 cases of acute myeloid leukemia (AML) and 15 cases of precursor T-cell acute leukemia (pT-ALL) was positive for CyCD22. The conclusion is made that united detection of CyCD79a and CyCD22 is the optimal immune combination for the diagnosis pB-ALL and the distinguishing pB-ALL with AML and pT-ALL.
Acute Disease ; B-Lymphocytes ; immunology ; Biomarkers, Tumor ; immunology ; CD79 Antigens ; immunology ; Cytoplasm ; immunology ; Flow Cytometry ; Humans ; Immunophenotyping ; Karyotyping ; Leukemia, Myeloid ; genetics ; immunology ; pathology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; metabolism ; pathology ; Sialic Acid Binding Ig-like Lectin 2 ; immunology

MYC rearrangement, a characteristic cytogenetic abnormality of Burkitt lymphoma and several subsets of other mature B-cell neoplasms, typically involves an immunoglobulin gene partner. Herein, we describe a case of precursor B-cell lymphoblastic leukemia harboring a MYC rearrangement with a novel non-immunoglobulin partner locus. The patient was a 4-yr-old Korean boy with ALL of the precursor B-cell immunophenotype. At the time of the second relapse, cytogenetic analyses revealed t(4;8)(q31.1;q24.1) as a clonal evolution. The MYC rearrangement was confirmed by FISH analysis. He died 3 months after the second relapse without achieving complete remission. To our knowledge, this is the first report of a case of MYC rearrangement with a non-immunoglobulin partner in precursor B-cell lymphoblastic leukemia.
Bone Marrow Cells/pathology ; Child, Preschool ; Chromosomes, Human, Pair 4 ; Chromosomes, Human, Pair 8 ; Genetic Loci ; Humans ; Immunoglobulins/genetics ; Karyotyping ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/metabolism/pathology ; Proto-Oncogene Proteins c-myc/*genetics ; Recurrence ; Translocation, Genetic

Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Chromosome Aberrations ; DNA Nucleotidylexotransferase ; metabolism ; Humans ; Immunoglobulin Light Chains ; metabolism ; Immunoglobulin Light Chains, Surrogate ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Lymphoma, T-Cell ; genetics ; metabolism ; pathology ; Membrane Glycoproteins ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins ; metabolism ; T-Cell Acute Lymphocytic Leukemia Protein 1

<b>OBJECTIVEb>To investigate the incidence of Philadelphia chromosome (Ph) in adult B-lineage acute lymphoblastic leukemia (B-ALL).

<b>METHODSb>One hundred and twelve adult patients with previously untreated B-ALL were prospectively investigated by interphase dual-color dual-fusion fluorescence in situ hybridization (DD-FISH) with two-color break apart probe BCR-ABL and the results were compared with that of conventional cytogenetics (CC).

<b>RESULTSb>The incidence of Ph chromosome was 17.98% (16/89) and 31.25% (35/112) by CC and DD-FISH, respectively. The mean positive rate of Ph+cells by FISH was 66.23% (ranging 18.5%-99%). Of the 35 Ph+ALL patients by FISH, 25 were successfully karyotyped by CC which included 5 normal karyotypes, 20 abnormal karyotypes including 16 Ph chromosome and 13 complex abnormalities.

<b>CONCLUSIONb>The incidence of Ph chromosome was 31.25% in adult with B-ALL. DD-FISH with BCR-ABL probe provides a powerful technique for the diagnosis of Ph+B-ALL. It is an important supplement to the CC analysis. DD-FISH technique should be used as a routine method for the diagnosis for adult acute B-ALL.

Adolescent ; Adult ; Aged ; B-Lymphocytes ; metabolism ; pathology ; Chromosome Aberrations ; Color ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Interphase ; Karyotyping ; Male ; Middle Aged ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; pathology

Translocations leading to fusions between the immunoglobulin heavy chain gene (IGH) and various partner genes have been reported in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, submicroscopic deletions within IGH in B-ALL have not been rigorously assessed. In this study, we investigated characteristics of IGH submicroscopic deletions, by FISH, in B-ALL with IGH rearrangements. FISH was performed by using commercially available IGH dual-color break-apart rearrangement probes (Abbott/Vysis, Downers Grove, IL, USA; Kreatech, Amsterdam, Netherlands). The study group included seven B-ALL patients with IGH rearrangements, observed by FISH. Among them, two exhibited deletion of the 5' variable region of IGH by FISH. The B-ALL in these two patients included two kinds of abnormal cells; one had an IGH rearrangement without any IGH submicroscopic deletion, while the other had an IGH submicroscopic deletion, which showed that one normal fusion signal and one 3' IGH signal were detected. Thus, submicroscopic deletion of the IGH 5' variable region may have occurred in either the native or rearranged chromosome 14. These findings indicate that B-ALL with IGH rearrangements may be accompanied by submicroscopic deletions of the IGH 5' variable region, which can be detected by FISH. The clinical significance of such deletions is unclear, but the loss of part of the IGH gene in B-ALL warrants further study.
Adult ; Child ; Female ; *Gene Deletion ; *Gene Rearrangement ; Humans ; Immunoglobulin Heavy Chains/*genetics ; In Situ Hybridization, Fluorescence ; Infant ; Male ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology ; Young Adult