Chikamasa Yoshida

A novel fusion variant of the MORF and CBP genes detected in therapy-related myelodysplastic syndrome with t(10;16)(q22;p13)

Summary. We report a case of therapy‐related myelodysplastic syndrome (t‐MDS) with t(10;16)(q22;p13), in which novel fusion transcripts of the MORF and CBP genes were detected. In one MORF–CBP fusion transcript, exon 15 of the MORF gene was fused in frame with exon 5 of the CBP gene. In a reciprocal CBP–MORF transcript, exon 4 of the CBP gene was fused in frame with exon 16 of the MORF gene. This is the first reported case of t‐MDS associated with t(10;16), and provides molecular evidence that the novel MORF–CBP and/or CBP–MORF fusion protein(s) might play an important role in the development of t‐MDS.

Peripheral blood circulating immature cell counts predict CD34+ cell yields in G-CSF-induced PBPC mobilization in healthy donors

BACKGROUND: It has been previously reported that the number of circulating immature cells (CIC) in peripheral blood (PB) estimates the number of CD34+ cells collected in G‐CSF plus chemotherapy‐induced PBPC mobilization. The correlation of CIC counts in PB with CD34+ cell yield and its usefulness was evaluated in G‐CSF‐induced PBPC mobilization for healthy donors.

A novel t(1;8)(q25;p11.2) translocation associated with 8p11 myeloproliferative syndrome

The 8p11 myeloproliferative syndrome is an aggressive neoplasm characterized by a myeloproliferative neoplasm associated with eosinophilia and lymphadenopathy, usually involving T or B lineage lymphoblastic lymphoma/leukaemia. The hallmark of this disease is the reciprocal translocations involving the fibroblast growth factor receptor 1 gene (FGFR1) on chromosome 8p11 and different gene partners. Thus, in the current 2008 World Health Organization (WHO) classification (Bain et al, 2008), 8p11 myeloproliferative syndrome is designated as a ‘myeloid and lymphoid neoplasm with eosinophilia and abnormalities of FGFR1’. The most common gene partner is ZMYM2 on chromosome 13q12, and more than 10 other partners have been identified (Jackson et al, 2010; Wasag et al, 2011). We here describe the novel translocation of t(1;8)(q25;p11.2) associated with 8p11 myeloproliferative syndrome, which was detected using a spectral karyotyping (SKY) technique.

Involvement of ERK1/2 and p38 MAP Kinase in Doxorubicin-Induced uPA Expression in Human RC-K8 Lymphoma and NCI-H69 Small Cell Lung Carcinoma Cells

We previously demonstrated the doxorubicin-induced urokinase-type plasminogen activator (uPA) expression in human RC-K8 lymphoma cells and NCI-H69 small cell lung carcinoma cells in which reactive oxygen species might be involved. Western blotting analysis revealed phosphorylation/activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) 1/2, p38 MAP kinase and stress-activated protein kinase/c-jun N-terminal protein kinase (SAPK/JNK) in doxorubicin-treated RC-K8 and H69 cells, and, therefore, we attempted to identify the MAP kinases implicated in doxorubicin-induced uPA expression by the use of their specific inhibitors. U0126, SB202190 and JNKI-1, inhibitors for MAPK kinase, (MEK) 1/2, p38 MAP kinase and SAPK/JNK, respectively, specifically and clearly inhibited their corresponding kinases. U0126 and SB202190, but not JNKI-1, almost completely inhibited the doxorubicin-induced uPA expression in both RC-K8 and H69 cells. However, U0126 rather enhanced the doxorubicin-induced activation of caspase-3 and poly ADP-ribose polymerase (PARP), and U0126 itself activated caspase-3 and PARP. Interestingly, JNKI-1 inhibited the doxorubicin-induced activation of caspase-3 and PARP. Therefore, doxorubicin treatment activates the above three kinases, but different MAP kinase signaling is responsible in the doxorubicin-induced caspase activation and expression of uPA. Thus, we could possibly manipulate the direction of doxorubicin-induced MAP kinase activation and the effects of doxorubicin on the tumor cell biology by the use of MAP kinase inhibitors.

Successful treatment with cyclosporin A of myelodysplastic syndrome with erythroid hypoplasia associated with t(6;8)(q15;q22)

We report a t(6;8)(q15;q22) in a patient with myelodysplastic syndrome (MDS) with erythroid hypoplasia. The patient was successfully treated with an immunosuppressive treatment with cyclosporin A, while the translocation was repeatedly detected as the sole anomaly with the percentages of positive cells ranging from 5% to 70%. To our knowledge, the t(6:8) has never been described in MDS.

Induction of urokinase-type plasminogen activator, interleukin-8 and early growth response-1 by STI571 through activating mitogen activated protein kinase in human small cell lung cancer cells

We previously demonstrated the simultaneous induction of urokinase-type plasminogen activator and interleukin-8, a CXC chemokine, in doxorubicin-treated human NCI-H69 small cell lung cancer cells in which extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase might be involved. NCI-H69 cells expressed one of the receptor tyrosine kinases, c-Kit, and STI571 inhibited the cell growth and stem cell factor-induced phosphorylation of c-Kit. We therefore investigated the effects of STI571 on the expression of urokinase-type plasminogen activator and interleukin-8 in NCI-H69 cells. Microarray analysis revealed the gene induction of not only urokinase-type plasminogen activator and interleukin-8, but also early growth response-1 in STI571-treated cells. Treatment with STI571 resulted in the induction of phosphorylation of all three mitogen-activated protein kinases, such as extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase and stress-activated protein kinase/c-jun N-terminal protein kinase. U0126, an inhibitor against extracellular signal-regulated kinase 1/2, however, only inhibited the STI571-induced interleukin-8 accumulation. Urokinase-type plasminogen activator and interleukin-8 are important biological factors in tumor cell regulation; STI571 may therefore influence many aspects of tumor cell biology through inducing urokinase-type plasminogen activator and interleukin-8, in which the induction of early growth response-1 expression and extracellular signal-regulated kinase 1/2 phosphorylation might be involved.