Establishment of a novel human acute myeloblastic leukemia cell line (YNH-1) with t(16;21), t(1;16) and 12q13 translocations

Abstract

The t(16;21)(p11;q22) translocation is a non-random chromothe fused FUS/ERG protein is shown to function as a transcripsomal aberration observed in several types of human acute tional regulator. 8,11 myeloblastic leukemia (AML), whereas the der(16)t(1;16) and On the other hand, the der (16) A 46-year-old male engineer was admitted to our hospital because of fever in June 1994. Peripheral blood examination Introduction showed white blood cells 120 × 10 9 /l with 91% myeloblasts, hemoglobin 8.3 g/dl and platelets 104 × 10 9 /l. Bone marrow Chromosomal translocations in specific subtypes of leukemia examination revealed 91% myeloblasts that were positive for are recognized to play an important role in the process of myeloperoxidase (MPO) but negative for ␣-naphthyl butylate leukemogenesis by synthesis of chimeric proteins. 1,2 The esterase (␣-NBE) and chloroacetate esterase (CAE) stainings. t(16;21)(p11;q22) translocation is one of the non-random There was no abnormal feature in the eosinophils or monochromosomal aberrations observed in human acute myelocytes. In surface marker analysis the blasts from bone marrow blastic leukemia (AML), blastic crisis of chronic myelogenous were positive for CD13 (79.5%), CD33 (93.3%) and CD34 leukemia (CML) and myelodysplastic syndrome (MDS) that (64.5%). Chromosome analysis of bone marrow cells showed progressed to AML. 3-10 AML with t(16;21) has been classified 46,XY, der(16)t(16;21)(p11;q22)t(1;16)(q12;q13), der (21) An induction therapy was started with enocitabine, daunoruberythrophagocytosis. 3,4 Clinical prognosis of AML with icin, 6-mercaptopurine and prednisolone and complete t(16;21) seems to be poor. Recently, molecular characterizremission (CR) was achieved with normal karyotype. Despite ation of this translocation has revealed that the FUS gene (also two courses of consolidation therapy, the patient relapsed called TLS) encoding an RNA-binding protein on chromosome after 3 months from remission. The second CR was obtained 16 is fused with the ERG gene, a member of the ets gene by low-dose etoposide and aclarubicin treatment in March superfamily, on chromosome 21 to produce the FUS/ERG 1995. However, the second relapse occurred after 1 month chimeric transcript. [7][8][9][10][11] As a result, the RNA-binding domain with blastoma in the colon. The patient died of progressive of FUS is replaced with the DNA-binding domain of ERG and disease and pneumonia in May 1995. CytokinesCorrespondence: H Hamaguchi, Department of Hematology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, TokyoAll cytokines used in this study, ie recombinant human gra-180, Japan

Dual Transforming Activities of the FUS (TLS)-ERG Leukemia Fusion Protein Conferred by Two N-Terminal Domains of FUS (TLS)

“…The enhanced expression of the G-CSF receptor in L-G cells induces their G-CSF-dependent proliferation like FUS-ERG and AML1-MTG8, although it does not inhibit the differentiation (40a). In addition, proliferation of a t(16;21) leukemia cell line, YNH-1, is stimulated by G-CSF (43). These findings suggest that the G-CSF receptor is one of target genes responsible for the oncogenic activity of FUS-ERG and that overexpression of the G-CSF receptor and resulting enhanced G-CSF signalling may contribute to the leukemogenesis of the t(16;21) leukemia.…”

The Oncogenic TLS-ERG Fusion Protein Exerts Different Effects in Hematopoietic Cells and Fibroblasts

“…One of the TLS alleles in these YNH-1 cells is fused to the ERG gene as a result of the t(16;21) translocation, and full-length TLS protein is expressed from the remaining intact allele (41). Since the anti-TLS antibody used in the Western blotting was raised against the N-terminal domain of TLS, it can detect the existence of both TLS and the TLS-ERG fusion protein in the YNH-1 nuclear extract (Fig.…”

“…To investigate the interactions of SR proteins with TLS and Pol II in TLS-ERG-positive tumor cells, we incubated the anti-SC35 antibody with nuclear extract from the YNH-1 acute myeloid leukemia cell line (41). One of the TLS alleles in these YNH-1 cells is fused to the ERG gene as a result of the t(16;21) translocation, and full-length TLS protein is expressed from the remaining intact allele (41).…”

TLS-ERG Leukemia Fusion Protein Deregulates Cyclin-Dependent Kinase 1 and Blocks Terminal Differentiation of Myeloid Progenitor Cells

“…YNH-1 is a human myeloid leukemia cell line established from peripheral blood of a leukemia patient carrying a t (16;21) translocation that generates the TLS-ERG fusion protein (15). The expression of the TLS-ERG gene in YNH-1 cells was confirmed by reverse transcription-PCR (Fig.…”

“…Human YNH-1 cells were kindly provided by Dr. Hiroyuki Hamaguchi (15) and cultured in RPMI 1640 with 10% fetal bovine serum, 10% horse serum, 1 mmol/L sodium pyruvate, 1% penicillin/streptomycin, 2 mmol/L L-glutamine, and 10 ng/mL recombinant human IL-3. BOSC23 retroviral packaging cells were obtained from American Type Culture Collection and maintained in DMEM supplemented with 10% FCS plus 0.025 mg/mL mycophenolic acid (Sigma) and 2.176 Ag/mL aminopterin (Sigma).…”