Establishment of five human malignant non-T lymphoid cell lines and mixed lymphocyte-tumor reaction.

Minegishi, Masayoshi; Tsuchiya, Shigeru; Minegishi, Naoko; Konno, Tasuke

doi:10.1620/tjem.151.283

Cited by 18 publications

(9 citation statements)

References 33 publications

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“…YCUB and KCB series of cell lines were sequentially established at Yokohama City University and Kanagawa Children’s Medical Center [ 21 ] and were provided in 2014 (H. Goto). THP series of cell lines, L-KUM and L-ASK, were sequentially established at Tohoku University [ 22 ] and were provided in 2014 (M. Minegishi). MB series of cell lines were sequentially established at Mie University Graduate School of Medicine [ 23 ] and were provided in 2014 (S. Iwamoto).…”

Section: Methodsmentioning

confidence: 99%

Anti-leukemic activity of bortezomib and carfilzomib on B-cell precursor ALL cell lines

et al. 2017

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Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response. Even in Ph-negative ALL cell lines, IKZF1 deletion and bilallelic loss of CDKN2A were independently associated with higher BTZ sensitivity. BTZ showed only marginal cross-resistance to four representative chemotherapeutic agents (vincristine, dexamethasone, l-asparaginase, and daunorubicin) in B-cell precursor-ALL cell lines. To improve the efficacy and safety of proteasome inhibitor combination chemotherapy, we also analyzed the anti-leukemic activity of carfilzomib (CFZ), a second-generation proteasome inhibitor, as a substitute for BTZ. CFZ showed significantly higher activity than BTZ in the majority of ALL cell lines except for the P-glycoprotein-positive t(17;19) ALL cell lines, and IKZF1 deletion was also associated with a favorable response to CFZ treatment. P-glycoprotein inhibitors effectively restored the sensitivity to CFZ, but not BTZ, in P-glycoprotein-positive t(17;19) ALL cell lines. P-glycoprotein overexpressing ALL cell line showed a CFZ-specific resistance, while knockout of P-glycoprotein by genome editing with a CRISPR/Cas9 system sensitized P-glycoprotein-positive t(17;19) ALL cell line to CFZ. These observations suggested that IKZF1 deletion could be a useful biomarker to predict good sensitivity to CFZ and BTZ, and that CFZ combination chemotherapy may be a new therapeutic option with higher anti-leukemic activity for refractory ALL that contain P-glycoprotein-negative leukemia cells.

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Section: Methodsmentioning

confidence: 99%

Anti-leukemic activity of bortezomib and carfilzomib on B-cell precursor ALL cell lines

et al. 2017

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“…Two pre-B ALL cell lines, TS-2 established from the peripheral blood of a 3-year-old female child and THP-4 with t(1;19)(q23;p13) and expression of the E2A-PBX1 chimeric gene, 8,9) were maintained in RPMI-1640 supplemented with 10% fetal bovine serum (FBS).…”

Section: Methodsmentioning

confidence: 99%

Identification of a novel fusion gene in a pre‐B acute lymphoblastic leukemia with t(1;19)(q23;p13)

et al. 2004

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The most common nonrandom translocation found among childhood pre-B acute lymphoblastic leukemias (ALL) is t(1;19)(q23;p13), which frequently results in fusion of E2A with PBX1. However, rare cases of childhood ALL and various other hematological diseases with t(1;19) lack the E2A-PBX1 fusion. Analyzing a cell line with pre-B-cell phenotype, TS-2, that carries t(1;19)(q23;p13) but lacks the E2A-PBX1 fusion, we successfully cloned the breakpoints, which fell within introns of MEF2D and DAZAP1. Both chimeric transcripts, MEF2D-DAZAP1 and DAZAP1-MEF2D, whose sequences indicated in-frame fusions between MEF2D and DAZAP1, were expressed in TS-2 cells and in bonemarrow cells of the patient from whom the TS-2 was established. MEF2D-DAZAP1 and DAZAP1-MEF2D proteins were both located in the nucleus, and MEF2D-DAZAP1 was able to form dimers with MEF2D and HDAC4. In addition, exogenous expression of MEF2D-DAZAP1 and DAZAP1-MEF2D promoted the growth of HeLa cells. Given the frequency of t(1;19) without the E2A-PBX1 fusion in hematological malignancies, we suggest that MEF2D/DAZAP1 rearrangements might be involved in the pathogenesis of those diseases. (Cancer Sci 2004; 95: 503-507) he most common type of childhood leukemia is acute lymphoblastic leukemia (ALL), which has a B-cell precursor phenotype.1) The main subtypes of ALL involve multiple genetic alterations including point mutations and deletions, and are also characterized by gross chromosomal changes such as translocations, which are likely to cause illegitimate recombination or juxtaposition of normally separated genes. In leukemias an in-frame fusion gene is often created, generating a hybrid protein with altered properties. Although more than 200 genes are known to be involved in translocations in leukemias, certain genes predominate in those events and the others are involved only rarely. 1)The most common nonrandom translocation in childhood pre-B ALL is t(1;19)(q23;p13), usually involving fusion between PBX1 at 1q23 and E2A at 19p13.3. The chimeric gene, E2A-PBX1, encodes a protein that contains the transactivation domain of E2A and the DNA-binding homeodomain of PBX1. 2)Although an identical E2A-PBX1 chimeric gene can be detected in more than 95% of ALL cases with t(1;19), in rare cases the E2A-PBX1 fusion gene is absent. 3,4)

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“…Seventy‐nine BCP‐ALL cell lines were analyzed, which included 14 Philadelphia chromosome‐positive (Ph+) cell lines (KOPN30bi, 55bi, 56, 57bi, 66bi, 72bi, 83bi, YAMN73, 91, KCB1, Nalm27, SU‐Ph2, TCCS, SK9), 11 MLL ‐rearranged ( MLL +) cell lines (KOPN1, KOPB26, KOCL33, 44, 45, 50, 51, 58, 69, YACL95, RS4;11), 16 t(1;19)‐ALL cell lines (KOPNK, 34, 36, 54, 60, 63, YAMN90, 92, YCUB6, YCUB8, Kasumi2, THP4, SCMCL1, 697, RCH, PreALP), 4 t(17;19)‐ALL cell lines (UOC‐B1, HALO1, YCUB2, Endo‐kun), 3 t(12;21)‐ALL cell lines (KOPN41, 79, Reh), and 31 other cell lines (KOS20, KOPN32, 39, 35, 41, 49, 61, 62, 68, 70, 71, 75, 79, 84, 85, KCB4, YAMN74, THP5, 7, 8, YCUB4, 5, 7, MBKG, MBMY, MBOK, L‐ASK, L‐KUM, SCMCL2, P30/OHK, Nalm6). Seven BCP‐ALL cell lines (RS4;11, 697, RCH, PreALP, UOC‐B1, Reh, and Nalm6) were established from non‐Japanese patients, whereas seventy‐two BCP‐ALL cell lines were established from Japanese patients , All cell lines were maintained in RPMI1640 medium supplemented with 10% fetal calf serum in a humidified atmosphere of 5% CO 2 at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…and 31 other cell lines (KOS20, KOPN32, 39, 35, 41, 49, 61, 62, 68, 70, 71, 75, 79, 84, 85, KCB4, YAMN74, THP5, 7, 8, YCUB4, 5, 7, MBKG, MBMY, MBOK, L-ASK, L-KUM, SCMCL2, P30/OHK, Nalm6). Seven BCP-ALL cell lines (RS4;11, 697, RCH, PreALP, UOC-B1, Reh, and Nalm6) were established from non-Japanese patients, whereas seventy-two BCP-ALL cell lines were established from Japanese patients [16][17][18][19], All cell lines were maintained in RPMI1640 medium supplemented with 10% fetal calf serum in a humidified atmosphere of 5% CO 2 at 37°C.…”

Section: Introductionmentioning

confidence: 99%

Clofarabine exerts antileukemic activity against cytarabine‐resistant B‐cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression

et al. 2018

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Cytosine arabinoside (Ara‐C) is one of the key drugs for the treatment of acute myeloid leukemia. It is also used for consolidation therapy of acute lymphoblastic leukemia (ALL). Ara‐C is a deoxyadenosine analog and is phosphorylated to form cytosine arabinoside triphosphate (Ara‐CTP) as an active form. In the first step of the metabolic pathway, Ara‐C is phosphorylated to Ara‐CMP by deoxycytidine kinase (DCK). However, the current cumulative evidence in the association of the Ara‐C sensitivity in ALL appears inconclusive. We analyzed various cell lines for the possible involvement of DCK in the sensitivities of B‐cell precursor ALL (BCP‐ALL) to Ara‐C. Higher DCK expression was associated with higher Ara‐C sensitivity. DCK knockout by genome editing with a CRISPR‐Cas9 system in an Ara‐C‐sensitive‐ALL cell line induced marked resistance to Ara‐C, but not to vincristine and daunorubicin, indicating the involvement of DCK expression in the Ara‐C sensitivity of BCP‐ALL. DCK gene silencing due to the hypermethylation of a CpG island and reduced DCK activity due to a nonsynonymous variant allele were not associated with Ara‐C sensitivity. Clofarabine is a second‐generation deoxyadenosine analog rationally synthesized to improve stability and reduce toxicity. The IC50 of clofarabine in 79 BCP‐ALL cell lines was approximately 20 times lower than that of Ara‐C. In contrast to Ara‐C, although the knockout of DCK induced marked resistance to clofarabine, sensitivity to clofarabine was only marginally associated with DCK gene expression level, suggesting a possible efficacy of clofarabine for BCP‐ALL that shows relative Ara‐C resistance due to low DCK expression.

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Establishment of five human malignant non-T lymphoid cell lines and mixed lymphocyte-tumor reaction.

Cited by 18 publications

References 33 publications

Anti-leukemic activity of bortezomib and carfilzomib on B-cell precursor ALL cell lines

Anti-leukemic activity of bortezomib and carfilzomib on B-cell precursor ALL cell lines

Identification of a novel fusion gene in a pre‐B acute lymphoblastic leukemia with t(1;19)(q23;p13)

Clofarabine exerts antileukemic activity against cytarabine‐resistant B‐cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression

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