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

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

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

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

<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

<b>OBJECTIVEb>To study the expression of zinc finger protein X-linked (ZFX) in bone marrow mononuclear cells (BMMCs) of children with B lineage acute lymphoblastic leukemia (B-ALL) and its relationship with prognosis.

<b>METHODSb>The expression of ZFX in human leukemia cell lines (REH, HL-60, NB(4) and K562) was measured by Western blot. ZFX gene was cloned by PCR from one patient and DNA sequencing technology was used to confirm it. Real-time PCR was used for detecting ZFX mRNA expression in the BMMCs of 82 children with newly-diagnosed B-ALL, 24 children with complete remission (CR) after induction therapy and 64 control children (fracture or congenital heart disease patients). According to the presence of bone marrow or central nervous system relapse during a follow-up of 3 years, the patients were identified as having a good or poor prognosis. Their ZFX mRNA levels in BMMCs at diagnosis were compared.

<b>RESULTSb>ZFX protein was expressed in human leukemia cell lines REH, HL-60, NB(4) and K562. ZFX mRNA expression was significantly higher in the newly-diagnosed ALL group than in the control group (P < 0.01). ZFX mRNA expression in the ALL CR group was significantly reduced compared with the newly-diagnosed ALL group (P < 0.01). Children with a poor prognosis had significantly higher ZFX mRNA levels at diagnosis than those with a good prognosis (P < 0.05).

<b>CONCLUSIONSb>ZFX is over-expressed in children with B-ALL and its levels are higher in those with a poor prognosis than those with a good prognosis, which suggests that ZFX is important in the prognosis evaluation of B-ALL.

Adolescent ; Cell Line, Tumor ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Kruppel-Like Transcription Factors ; analysis ; genetics ; physiology ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Prognosis ; Real-Time Polymerase Chain Reaction

<b>OBJECTIVEb>MDM2 is considered a proto-oncogene due to its ability to inhibit P53 tumor-suppressor function. But, evidence showed that MDM2 might have a P53-independent role in tumorigenesis. MDM2 is over-expressed in human sarcoma and carcinoma. Recent studies showed that MDM2 might act as a transcriptional factor to modulate expressions of other genes involved in cell cycle regulation and transformation. In the present study, the investigators hypothesized that MDM2 directly affected NF-kappaB expression and function in a P53-independent manner.

<b>METHODSb>MDM2 was transfected to acute lymphoblastic leukemia (ALL) line EU-4 cells lacking P53 expression and expressing very low levels of MDM2. MDM2 and P65 expression in mRNA level and protein level were detected by Western blot and Northern blot after transfection. Since the expression of E-selectin is P65 dependent, E-selectin promoter-CAT construct and P65 and MDM2 expression plasmids were co-transfected to EU-4 cells. CAT activation was determined with ELISA. The effect of adriamycin (ADM) at the concentrations of 15 micro g/ml, 7.5 micro g/ml, 5 micro g/ml and 1 micro g/ml on MDM2-transfected EU-4 cells and the parent cells was detected by MTT assay.

<b>RESULTSb>The results showed that MDM2 up-regulated P65 expression at both mRNA and protein levels, and MDM2 increased P65-mediated transactivation of E-selectin promoter. Without P65, MDM2 had no effect on the transactivation of E-selectin. Moreover, MDM2 antisense could not change the transactivation of E-selectin. MTT results showed that the survival rate of MDM2 transfected EU-4 cells was higher than that of parental cells. The results suggested that MDM2 transfection increase drug resistance of EU-4 cells to ADM compared with parent cells.

<b>CONCLUSIONb>(1) MDM2 up-regulated transcriptionally P65 expression. (2) MDM2 increased drug resistance of leukemia cells to ADM. (3) MDM2 elevated NF-kappaB activity in a P53-independent manner in childhood lymphoblastic leukemia cell line.

Antibiotics, Antineoplastic ; therapeutic use ; Blotting, Northern ; Blotting, Western ; Cell Line, Tumor ; drug effects ; Child ; Doxorubicin ; therapeutic use ; Drug Resistance, Neoplasm ; physiology ; Enzyme-Linked Immunosorbent Assay ; Humans ; NF-kappa B ; genetics ; metabolism ; Nuclear Proteins ; genetics ; physiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins ; genetics ; physiology ; Proto-Oncogene Proteins c-mdm2 ; RNA, Messenger ; genetics ; metabolism ; Transcription Factor RelA ; Transfection ; methods

In order to investigate the effect of N-tosyl-L-phenylalnylchloromethyl ketone (TPCK) and dexamethasone (Dex) on expression of nuclear transcription factor-kappaB (NF-kappaB) in childhood acute lymphoblastic leukemia (ALL) and its significance, so as to provide the experimental basis for corresponding clinical treatment of ALL, in which NF-kappaB is taken as a target. The biotin-streptavidin method was used to detect the expression of NF-kappaB P65 protein and the effects of TPCK and Dex at clinically relevant dosage on activity of NF-kappaB P65 protein in 20 childhood ALL patients. The results indicated that the expression of NF-kappaB P65 protein was strongly diminished and reached to negative level at 2 hours by treatment with 40 micromol/L TPCK, the positive expression of NF-kappaB P65 protein was (2.5 +/- 1.6)%. TPCK had a time-dependent inhibitory effect on ALL cells cultured in vitro. The expression of NF-kappaB P65 protein in ALL cells was strongly inhibited by clinically relevant concentration of dexamethasone 5.0 microg/ml for 24 hours in vitro. The positive expression was (25.0 +/- 3.0)%, there was significant difference, as compared with untreated ALL cells (T=55, P<0.01). It is concluded that TPCK and Dex can inhibit NF-kappaB activity. Inhibition of NF-kappaB activity may be one of the effect mechanism of dexamethasone on ALL cells. Inhibition of NF-kappaB conduction pathway may have a significant value in childhood ALL treatment.
Bone Marrow Cells ; pathology ; Cells, Cultured ; Child ; Child, Preschool ; Dexamethasone ; pharmacology ; Female ; Humans ; Infant ; Leukocytes, Mononuclear ; pathology ; Male ; NF-kappa B ; biosynthesis ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Protein Synthesis Inhibitors ; pharmacology ; Tosylphenylalanyl Chloromethyl Ketone ; pharmacology ; Tumor Cells, Cultured

In B lymphoblastic leukemia/lymphoma (B-ALL/LBL), t(9;22)(q34;q11.2) and t(1;19)(q23;p13.3) are recurrent cytogenetic abnormalities. The concurrent occurrence of both abnormalities is very rare, and only 3 cases have been previously reported. Here, we report a case of adult B-ALL with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3). A literature review revealed that ider(9) (q10)t(9;22) is a rare variant of t(9;22) with a deletion of the short arm of chromosome 9. Fifteen cases of ider(9)(q10)t(9;22) have been reported. This abnormality is specific to precursor B-lymphoid neoplasms, such as B-ALL or B-lymphoid blast phase of CML, and is associated with disease progression or short survival. The cytogenetic abnormality t(1;19) is also specific to B-ALL. In most instances of t(1;19), TCF3 is fused to PBX1; however, a few cases have identical translocations but no TCF3-PBX1 fusion, as was observed in our patient. We describe the first case of ider(9)(q10)t(9;22) in combination with TCF3-PBX1 negative t(1;19). The patient underwent imatinib therapy in addition to intensive chemotherapy, but failed to achieve remission.
Bone Marrow Cells/cytology/pathology ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 19 ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 9 ; Female ; Fusion Proteins, bcr-abl/genetics/metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics ; *Translocation, Genetic