CXCR2 inhibition overcomes ponatinib intolerance by eradicating chronic myeloid leukemic stem cells through PI3K/Akt/mTOR and dipeptidylpeptidase Ⅳ (CD26).

This study explores the therapeutic potential of targeting CXCR2 in patients afflicted with ponatinib-resistant chronic myeloid leukemia (CML). Ponatinib, a third-generation tyrosine kinase inhibitor (TKI), was initially designed for treating patients with CML harboring the T315I mutation. However, resistance or intolerance issues may lead to treatment discontinuation.

Generation of the human pluripotent stem cell lines KUMi005-A from a patients with multiple myeloma.

Multiple myeloma (MM) progresses with abnormal monoclonal proliferation and accumulation of malignant plasma cells in the bone marrow. We established human induced pluripotent stem cells (iPSCs), KUMi005-A, from bone marrow samples of a patient with MM. This reprogrammed cell line has similar characteristics to human embryonic stem cells, such as proliferation properties and pluripotency.

Generation of human induced iPSC KUMi003-A from acute promyelocytic leukemia (APL) M3.

Acute promyelocytic leukemia (APL) M3 is an acute myeloid leukemia (AML) subtype and is characterized by the chromosomal translocation t(15;17)(p22;q11), which results in the fusion of the promyelocytic gene (PML) at 15q22 with the retinoic acid α-receptor gene (RARA) at 17q21. We generated an induced pluripotent stem cell line "KUMi003-A" from an APL M3 patient that is pluripotent and can differentiate into the three germ layers. This iPSC line will be useful as a disease model to investigate disease mechanisms specific to APL M3.

PVR (CD155) Expression as a Potential Prognostic Marker in Multiple Myeloma.

Poliovirus receptor (PVR, CD155) is upregulated during tumor progression, and PVR expression is associated with poor prognosis in cancer patients; however, prognostic implications for PVR in multiple myeloma (MM) have not been investigated. PVR plays an immunomodulatory role by interacting with CD226, CD96, and TIGIT. TIGIT is a checkpoint inhibitory receptor that can limit adaptive and innate immunity, and it binds to PVR with the highest affinity.

Generation of a human induced pluripotent stem cell line KUMi006 from a patient with multiple myeloma.

In this study, we report the generation of a novel human induced pluripotent stem cell (hiPSC) line from bone marrow mononuclear cells of a patient with multiple myeloma, using an integrative Sendai virus vector. This pluripotent cell line has been shown to differentiate into three germ layers. Therefore, these induced pluripotent stem cells (iPSCs) will enable not only advances in cell therapy products but also the study of mechanisms.

Regulation of sclerostin by the SIRT1 stabilization pathway in osteocytes.

Osteocytes play a critical role in bone remodeling through the secretion of paracrine factors regulating the differentiation and activity of osteoblasts and osteoclasts. Sclerostin is a key osteocyte-derived factor that suppresses bone formation and promotes bone resorption, therefore regulators of sclerostin secretion are a likely source of new therapeutic strategies for treatment of skeletal disorders. Here, we demonstrate that protein kinase CK2 (casein kinase 2) controls sclerostin expression in osteocytes via the deubiquitinase ubiquitin-specific peptidase 4 (USP4)-mediated stabilization of Sirtuin1 (SIRT1).

A human pluripotent stem cell line KUMi004-A generated from a patient with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a type of blood cancer caused by the abnormal accumulation of malignant plasma cells. In this study, we generated CLL iPSCs (KUMi004-a) using the Sendai virus, confirming pluripotency. Also, it can differentiate into three primary germ layers.

Generation of induced pluripotent stem cell line KUMi002-A with normal karyotype from a patient with Philadelphia chromosome-positive chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is caused by the dysregulated tyrosine kinase activity of the BCR-ABL fusion protein. In this study, we generated induced pluripotent stem cells (iPSCs) with a normal karyotype, using cells from a patient with CML and a Philadelphia chromosome. These human iPSCs showed positive pluripotency markers and differentiated into three germ layers.

Generation of the induced pluripotent stem cell line KUMi001-A carrying the Philadelphia chromosome from a chronic myeloid leukemia patient.

Chronic myeloid leukemia (CML) is caused by the BCR-ABL fusion protein, which dysregulates tyrosine kinase activity. In this study, we generated induced pluripotent stem cells (iPSCs) carrying the Philadelphia chromosome from a CML patient with the BCR-ABL fusion protein. CML iPSCs were positive for pluripotency markers and had the ability to differentiate into the three germ layers.

Prognostic Value of Galectin-9 Relates to Programmed Death-Ligand 1 in Patients With Multiple Myeloma.

Galectin-9 (Gal-9) expression can be negatively or positively associated with cancer patient prognosis, depending on the cancer type. However, the nature of this relationship remains unclear in multiple myeloma. Therefore, we evaluated the prognostic value of Gal-9 and its relationship with the expression of PD-L1 molecule, the most widely studied immune checkpoint inhibitor, in patients with newly diagnosed multiple myeloma.

CXCR2, a novel target to overcome tyrosine kinase inhibitor resistance in chronic myelogenous leukemia cells.

Chronic myeloid leukemia (CML) is a reciprocal translocation disorder driven by a breakpoint cluster region (BCR)-Abelson leukemia virus (ABL) fusion gene that stimulates abnormal tyrosine kinase activity. Tyrosine kinase inhibitors (TKIs) are effective in treating Philadelphia chromosome (Ph) + CML patients. However, the appearance of TKI-resistant CML cells is a hurdle in CML treatment.

Generation of normal induced pluripotent stem cell line KUMCi002-A from bone marrow CD34+ cells of patient with multiple myeloma disease having 13q deletion and IGH translocation.

Multiple myeloma (MM) is a hematological cancer characterized by an uncontrolled proliferation of antibody-secreting plasma cells within the bone marrow. Currently, cell therapy such as chimeric antigen receptor T-cell (CAR-T) based on induced pluripotent stem cells (iPSCs) has received attention for treating MM. However, the generation of iPSCs from MM patients appears to be very rarely reported.

Supporting data on enhanced reprogramming of human CD34+ hematopoietic stem cells to induced pluripotent stem cells using human placenta-derived cell conditioned medium.

The data presented herein support "Generation of an induced pluripotent stem cell line KUMCi001-A from CD34+ bone marrow cells of a patient with acute lymphoblastic leukemia using human placenta-derived cell conditioned medium." The supplementary data were as follows. (1) Comparison of reprogramming efficiency of human placenta-derived cell conditioned medium with defined medium (mTeSR™1) and the generation of induced pluripotent stem cells (iPSCs) from a patient with acute lymphoblastic leukemia (ALL) with significantly higher reprogramming efficiency than that of the defined medium ( ≤ 0.

Generation of an induced pluripotent stem cell line KUMCi001-A from CD34+ bone marrow cells of a patient with acute lymphoblastic leukemia using human placenta-derived cell conditioned medium.

Many patients with acute lymphoblastic leukemia (ALL) show relapse post-chemotherapy. Therefore, it is important to develop a human induced pluripotent stem cell (hiPSC) line from ALL cells to verify the pathophysiology. However, the low efficiency of the established reprogramming protocol has hampered the development of ALL hiPSC lines.

Bone-Targeting AAV-Mediated Gene Silencing in Osteoclasts for Osteoporosis Therapy.

Improper activity of bone-resorbing osteoclasts results in low bone density and deterioration of bone structure, which increase the risk of fractures. Anti-resorptive therapies targeting osteoclasts have proven effective in preserving bone mass, but these therapeutic agents lead to defective new bone formation and numerous potential side effects. In this study, we demonstrate that recombinant adeno-associated virus, serotype 9 (rAAV9) can deliver to osteoclasts an artificial microRNA (amiR) that silences expression of key osteoclast regulators, RANK (receptor activator for nuclear factor κB) and cathepsin K (rAAV9.

CXCR2 Ligands and mTOR Activation Enhance Reprogramming of Human Somatic Cells to Pluripotent Stem Cells.

Induced pluripotent stem cell (iPSC) technology has great promise in regenerative medicine and disease modeling. In this study, we show that human placenta-derived cell conditioned medium stimulates chemokine (C-X-C motif) receptor 2 (CXCR2) in human somatic cells ectopically expressing the pluripotency-associated transcription factors , , , and (OSKM), leading to mechanistic target of rapamycin (mTOR) activation. This causes an increase in endogenous cMYC levels and a decrease in autophagy, thereby enhancing the reprogramming efficiency of human somatic cells into iPSCs.

CXCR2 and its related ligands play a novel role in supporting the pluripotency and proliferation of human pluripotent stem cells.

Basic fibroblast growth factor (bFGF) is a crucial factor sustaining human pluripotent stem cells (hPSCs). We designed this study to search the substitutive factors other than bFGF for the maintenance of hPSCs by using human placenta-derived conditioned medium without exogenous bFGF (hPCCM-), containing chemokine (C-X-C motif) receptor 2 (CXCR2) ligands, including interleukin (IL)-8 and growth-related oncogene α (GROα), which were developed on the basis of our previous studies. First, we confirmed that IL-8 and/or GROα play independent roles to preserve the phenotype of hPSCs.

Human feeder cells can support the undifferentiated growth of human and mouse embryonic stem cells using their own basic fibroblast growth factors.

In the culture system using human feeder cells, the mechanism through which these cells support undifferentiated growth of embryonic stem cells (ESCs) has not been well investigated. Here, we explored the mechanisms of 3 kinds of human feeder cells, including human placental cells from the chorionic plate, human bone marrow stromal cells, and human foreskin fibroblasts. First, we determined that undifferentiated growth of 2 kinds each of human (H1 and HSF6) and mouse (D3 and CE3) ESCs was possible in all human feeder cell types tested (human placental cells, human bone marrow stromal cells, and human foreskin fibroblasts), without the need for exogenous cytokine supplementation including basic fibroblast growth factor (bFGF) and leukemia inhibitory factor.