Establishment and characterization of a new permanent cell line (GDM-1) from a patient with myelomonoblastic leukemia

Ben‐Bassat, Hannah; Korkesh, Aviva; Voss, R.; Leizerowitz, Rachel; Polliack, Aaron

doi:10.1016/0145-2126(82)90055-8

Cited by 27 publications

(16 citation statements)

References 28 publications

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“…Leukaemia-derived cell lines are a useful tool for the study of genome organisation in relation to gene expression in this pathology. In particular, the AML-derived cell line GDM-1 [Ben-Bassat et al, 1982] was already subject of investigations that showed overexpression of the HLXB9 gene [Nagel et al, 2005]. This cell line harbours a translocation between chromosomes 6 and 7, precisely t(6; 7)(q23;q36), with the breakpoint in chromosome 7 distal to HLXB9 and upstream of MYB at 6q23, a gene often activated in leukaemia [Nagel et al, 2005;Kamel et al, 2014].…”

Section: Concettamentioning

confidence: 99%

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Nuclear Repositioning of the Non-Translocated HLXB9 Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

Federico

Leotta²,

Bruno³

et al. 2017

Cytogenet Genome Res

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Transcriptionally active and inactive topologically associated domains (TADs) occupy different areas in the cell nucleus, and chromosomal rearrangements relocating TADs could determine ectopic expression of the repositioned genes. In this study, we investigated the HLXB9 gene in a myeloid leukaemia cell line, GDM-1, known to harbour a rearrangement involving chromosome 7 with a breakpoint distal to HLXB9, highly expressed in these cells. We used FISH to target the regions involved in the translocation and to distinguish the translocated chromosome from the non-translocated one in interphase nuclei. Two-dimensional analysis of the interphase FISH data indicated that the 2 HLXB9 alleles had a different localisation in the cell nuclei, with the translocated allele consistently positioned in the nuclear periphery and the normal one in the more internal portion of the nucleus, known as the transcriptionally active compartment. Our data may indicate that HLXB9 transcripts in the GDM-1 cell line do not arise from the allele located in rearranged chromosome 7, suggesting that regulation of gene expression in cancer cells harbouring chromosomal translocations might be more complex than previously thought, paving the path to further investigations on mechanisms of gene expression.

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Section: Concettamentioning

confidence: 99%

“…HTL01008) was grown at 37 ° C and 5% CO 2 , in RPMI 1640 supplemented with FBS to a final concentration of 20%, 1% penicillin/streptomycin and 1% Lglutamine [Ben-Bassat et al, 1982].…”

Section: Cell Culturesmentioning

confidence: 99%

Nuclear Repositioning of the Non-Translocated HLXB9 Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

Federico

Leotta²,

Bruno³

et al. 2017

Cytogenet Genome Res

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“…GDM1, derived from a patient with an acute myelomonocytic transformation of a Philadelphianegative myeloproliferative disorder, 25 showed a markedly reduced proliferation when exposed to imatinib. Mutational analysis of known imatinib targets revealed a missense mutation within exon 12 of CSF1R that results in a Y571D amino-acid change.…”

Section: Discussionmentioning

confidence: 99%

Imatinib sensitivity as a consequence of a CSF1R-Y571D mutation and CSF1/CSF1R signaling abnormalities in the cell line GDM1

et al. 2008

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Imatinib is usually a highly effective treatment for myeloproliferative neoplasms (MPNs) associated with ABL, PDGFRA or PDGFRB gene fusions; however, occasional imatinibresponsive patients have been reported without abnormalities of these genes. To identify novel imatinib-sensitive lesions, we screened 11 BCR-ABL-negative cell lines and identified GDM1, derived from a patient with an atypical MPN (aMPN), as being responsive to imatinib. Screening of genes encoding known imatinib targets revealed an exon 12 mutation in the colonystimulating factor 1 receptor (CSF1R; c-FMS) with a predicted Y571D amino-acid substitution. CSF1R in GDM1 was constitutively phosphorylated, but rapidly dephosphorylated on exposure to imatinib. Y571D did not transform FDCP1 cells to growth factor independence, but resulted in a significantly increased colony growth compared with controls, constitutive CSF1R phosphorylation and elevated CSF1R signaling. We found that GDM1 expresses CSF1, and CSF1 neutralization partially inhibited proliferation, suggesting the importance of both autocrine and intrinsic mechanisms of CSF1R activation. An extensive screen of CSF1R in aMPNs and acute myeloid leukemia identified three additional novel missense variants. None of these variants were active in transformation assays and are therefore likely to be previously unreported rare polymorphisms or non-pathogenic passenger mutations.

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“…GDM-1 cells [19] were maintained in the same media supplemented with GM-CSF (2 ng/mL; R&D, Minneapolis, MN, USA). HL-60 [20], NB4 [21], and TF-1 [22] cells were maintained as previously described [23].…”

Section: Methodsmentioning

confidence: 99%

AKT Signaling as a Novel Factor Associated with In Vitro Resistance of Human AML to Gemtuzumab Ozogamicin

et al. 2013

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Gemtuzumab ozogamicin (GO), an immunoconjugate between an anti-CD33 antibody and a calicheamicin-γ1 derivative, induces remissions and improves survival in a subset of patients with acute myeloid leukemia (AML). As the mechanisms underlying GO and calicheamicin-γ1 resistance are incompletely understood, we herein used flow cytometry-based single cell network profiling (SCNP) assays to study cellular responses of primary human AML cells to GO. Our data indicate that the extent of DNA damage is quantitatively impacted by CD33 expression and drug efflux activity. However, although DNA damage is required for GO-induced cytotoxicity, it is not sufficient for effective cell kill, suggesting that downstream anti-apoptotic pathways may function as relevant resistance mechanisms. Supporting this notion, we found activated PI3K/AKT signaling to be associated with GO resistance in vitro in primary AML cells. Consistently, the investigational AKT inhibitor MK-2206 significantly sensitized various human AML cells to GO or free calicheamicin-γ1 with particularly pronounced effects in otherwise GO or free calicheamicin-γ1 -resistant cells. Likewise, MK-2206 also sensitized primary AML cells to calicheamicin-γ1. Together, our findings illustrate the capacity of SCNP assays to discover chemotherapy-related biological pathways and signaling networks relevant to GO-induced genotoxic stress. The identification of AKT signaling as being associated with GO resistance in vitro may provide a novel approach to improve the in vivo efficacy of GO/calicheamicin-γ1 and, by extrapolation, other DNA damage-based therapeutics.

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Establishment and characterization of a new permanent cell line (GDM-1) from a patient with myelomonoblastic leukemia

Cited by 27 publications

References 28 publications

Nuclear Repositioning of the Non-Translocated <b><i>HLXB9</i></b> Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

Nuclear Repositioning of the Non-Translocated <b><i>HLXB9</i></b> Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

Imatinib sensitivity as a consequence of a CSF1R-Y571D mutation and CSF1/CSF1R signaling abnormalities in the cell line GDM1

AKT Signaling as a Novel Factor Associated with In Vitro Resistance of Human AML to Gemtuzumab Ozogamicin

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