Cloning of a newly identified heart-specific troponin I isoform, which lacks the troponin T binding portion, using the yeast hybrid system.

Objective: To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection.

Adhesion to fibronectin induces megakaryocytic differentiation of JAS-REN cells.

Background: Binding of integrins to the extracellular matrix elicits various responses. We have previously reported a megakaryocytic-erythroid cell line (JAS-R) that showed phenotypic changes after adhesion to plastic dishes. However, the matrix protein and the mechanism responsible for megakaryocytic differentiation still remain unknown.

MLF1-interacting protein is mainly localized in nucleolus through N-terminal bipartite nuclear localization signal.

Background: The myelodysplasia/myeloid leukemia factor 1-interacting protein (MLF1LP, also called KLIP1 and CENP-50) is reported to localize in both the nucleus and the cytoplasm. To investigate the functions of MLF1IP, its subnuclear localization was studied.

Materials And Methods: MLF1IP was tagged with green fluorescent protein (EGFP).

Segregation of megakaryocytic or erythroid cells from a megakaryocytic leukemia cell line (JAS-R) by adhesion during culture.

Adhesion is one of the important biologic characteristics of leukemic cells. We previously reported a new megakaryocytic-erythroid cell line, JAS-R. In this study, JAS-R cells were segregated into two types by the differences of attachment to culture dishes.

Diffuse large B-cell lymphoma arising independently to lymphoplasmacytic lymphoma: a case of two lymphomas.

Richter's syndrome occurs in 5-10% of patients with chronic lymphocytic leukemia, either by transformation of the primary neoplastic lymphocyte, or as a distinct B-cell neoplasm. We report a Japanese patient with lymphoplasmacytic lymphoma in whom a diffuse large B-cell lymphoma developed after treatment with rituximab. Molecular examination on immunoglobulin VH genes revealed that the lymphomas had arisen in two separate clones.

JAS-R, a new megakaryo-erythroid leukemic cell line that secretes erythropoietin.

Background: The processes of leukemogenesis and differentiation of the megakaryo-erythroid lineage remain poorly understood. Leukemic cell lines derived from megakaryocytic leukemia are valuable reagents for studies on these events.

Materials And Methods: A new cell line, JAS-R, was established from a 64-year-old patient with acute megakaryocytic leukemia (AML M7).

Depsipeptide-resistant KU812 cells show reversible P-glycoprotein expression, hyper-acetylated histones, and modulated gene expression profile.

Depsipeptide (FK228), a histone deacetylase inhibitor, is a promising new anticancer agent. The mechanism of resistance to this agent was studied using KU812 cells. Depsipeptide-resistant KU812 cells expressed P-glycoprotein (P-gp) and their resistance was abolished by co-treatment with verapamil.

Pretreatment with interferon-alpha radiosensitizes Daudi cells modulating gene expression and biomarkers.

Background: Interferon (IFN) potentiates cytotoxicity by X-ray irradiation. To elucidate the mechanism of this potentiation, the biological markers related to DNA damage and cell survival were studied.

Materials And Methods: IFN-alpha-sensitive Daudi and its resistant cells were used.

Depsipeptide enhances imatinib mesylate-induced apoptosis of Bcr-Abl-positive cells and ectopic expression of cyclin D1, c-Myc or active MEK abrogates this effect.

Background: Imatinib mesylate (ST1571) is the first-line drugfor chronic myeloid leukemia (CML), but development of resistance to this drug is a clinical problem. To explore the effective use of ST1571, we studied the combination treatment with histone deacetylase inhibitor (depsipeptide, FK228).

Materials And Methods: FK228 and trichostatin A (TSA) were studied with respect to apoptosis of two Bcr-Abl-positive cell lines, K562 and TCC-S.

Ectopic cyclin D1 expression blocks STI571-induced erythroid differentiation of K562 cells.

Bcr-Abl tyrosine kinase inhibitor induces apoptosis and erythroid differentiation of K562 cells. During this erythroid differentiation, c-Myc and cyclin D1 transcripts are transiently downregulated. Accordingly, we studied the effect of cyclin D1 overexpression on erythroid differentiation.

Inactivation of ERK accelerates erythroid differentiation of K562 cells induced by herbimycin A and STI571 while activation of MEK1 interferes with it.

K562 cells contain a Bcr-Abl chimeric gene and differentiate into various lineages in response to different inducers. We studied the role of the mitogen-activated protein kinase (MAPK) kinase 1 (MEK1)/extracellular signal-regulated kinase (ERK) pathway during the erythroid differentiation of K562 cells induced by tyrosine kinase inhibitors (herbimycin A or STI571), using genetically modified cells (constitutively MEK1-activated K562: K562/MEK1, and inducible ERK-inactivated K562: K562/CL100). Basal expression of glycophorin A was markedly reduced in K562/MEK1 cells compared with that in parental cells, while it was augmented in K562/CL100 cells.

Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11).

The NUP98 gene is involved in several chromosomal abnormalities associated with acute leukemia. The recurrent t(11;20)(p15;q11) chromosomal translocation results in generation of the NUP98/TOP1 chimeric gene. This abnormality has been observed primarily in therapy-related leukemias, and TOP1/NUP98 transcripts have not been demonstrated.

DNA topoisomerase II inhibitor, etoposide, induces p21WAF1/CIP1 through down-regulation of c-Myc in K562 cells.

Background: Anticancer agents modulate gene expression and these changes are essential for tumor cell killing. To investigate the mechanism by which etoposide acts as an anticancer agent, the relationship between p21WAF1/CIP1 (p21) and c-Myc was studied.

Materials And Methods: K562 cells with and without ectopic c-Myc expression were studied.

Detection of MUC1 and keratin 19 mRNAs in the bone marrow by quantitative RT-PCR predicts the risk of distant metastasis in breast cancer patients.

Background: Early detection of micrometastasis in bone marrow is critical for the prognosis of breast cancer patients. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) has been used to detect cancer cells in bone marrow, but its utility as a prognostic factor still remains obscure.

Materials And Methods: Bone marrow samples were aspirated from the anterosuperior iliac spine of 34 patients, immediately after their surgical procedures had been completed.

No V(H) somatic hypermutation was detected in B-cells of a patient with macroglobulinemia due to splenic marginal zone lymphoma.

B-cell diseases are classified on the basis of the normal differentiation stages. We report here a case of a patient with a long history of leukocytosis, splenomegaly without lymphadenopathy, and hyperviscosity symptoms. Clinically, the patient's diagnosis was leukemic Waldenstrom macroglobulinemia.

Lack of BCL10 mRNA mutation in lymphold malignancies.

Background: BCL10, a gene involved in the chromosomal translocation t(1;14)(p22;q32) found in mucosa-associated lymphoid tissue lymphoma (MALT lymphoma), has shown mutation in not only MALT lymphomas but also other lymphold tumors. However, the mutation rate remains controversial. One possible reason is variation in the source material (DNA or RNA), with most studies having been done using tumor DNA.