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AP-1060

Cat.No.: CSC-C0596

Species: Human

Source: acute myeloid leukemia

Morphology: single round cells growing in suspension

Culture Properties: suspension

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Cat.No.
CSC-C0596
Description
Established from the bone marrow of a 45-year-old man with acute promyelocytic leukemia (APL = AML FAB M3) in fourth relapse in 1998; cells were immortalized using ethyl-nitrosourea; cells are described to be constitutively dependent on GM-CSF and IL-3 or G-CSF; cells carry and express the t(15;17)(q22;q11.2) PML-RARA fusion gene
Species
Human
Source
acute myeloid leukemia
Recommended Medium
70% SuperCult® IMDM + 20% h.i. FBS + 10% vol conditioned medium of cell line 5637
Culture Properties
suspension
Morphology
single round cells growing in suspension
Karyotype
Human near-diploid karyotype with 3% polyploidy - 46(42-47)<2n>XY, t(3;14)(p21;q11.2), add(5)(q33), del(6)(q25), add(12)(p13), t(15;17)(q22;q21); carries t(15;17) with rearrangement of PML and RARA; resembles published karyotype
Quality Control
Mycoplasma: negative in microbiological culture, PCR assays
Immunology: CD3 -, CD13 +, CD14 -, CD19 -, CD33 +, HLA-DR -
Viruses: PCR: EBV -, HBV -, HCV -, HIV -, HTLV-I/II -, SMRV -
Storage and Shipping
Frozen with 70% medium, 20% FBS, 10% DMSO at about 4 x 10^6 cells/ampoule; ship in dry ice; store in liquid nitrogen
Citation Guidance
If you use this products in your scientific publication, it should be cited in the publication as: Creative Bioarray cat no. If your paper has been published, please click here to submit the PubMed ID of your paper to get a coupon.

AP-1060 is a human acute promyelocytic leukemia (APL) cell line established by Sun et al. in 2004 from bone marrow aspirate of a 45-year-old male with clinical resistance to both all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). AP-1060 is a naturally ATRA/ATO dual-resistant model, which is important for understanding the mechanism of APL drug resistance. AP-1060 cells grow in vitro in a suspension form and morphologically remain promyelocytes with large cell bodies, round to indented nuclei, ample cytoplasm with coarse azurophilic granules, and obvious Auer rods.

Molecularly, AP-1060 maintains the classical t(15;17)(q22;q11) translocation which produces the PML-RARA fusion gene. However, p.Pro408Ser mutation (p.Pro900Ser in the fusion protein) was identified in the RARA moiety which blocks the ATRA-induced transcriptional activation. In addition, the cell line was found to acquire a rare secondary t(3;14)(p21.1;q11.2) translocation with the formation of an ETV6-NTRK3 (EN) fusion and homozygous deletion of WT1. These changes are suspected to play a role in drug-resistance acquisition and myeloid transformation potential.

ATRA-Resistant APL Cells are Phenotypically and Mechanically Distinct

Although all-trans retinoic acid (ATRA) is a critical drug for the treatment of acute promyelocytic leukemia (APL), an aggressive form of acute myeloid leukemia, almost 20% of APL patients are resistant to ATRA. As no biomarkers for ATRA resistance are yet available, using mechano-node-pore sensing, a single-cell mechanical phenotyping platform, and patient-derived APL cell lines NB4 (ATRA-sensitive) and AP-1060 (ATRA-resistant), Brain et al. explored whether cell mechanics could be linked to this pathological phenotype.

NB4 and AP-1060 cells were cultured in media with ATRA at concentrations ranging from 10 nM to 10 µM and their differentiation was measured. Flow cytometry revealed that NB4 cells were sensitive to ATRA treatment, while AP-1060 cells were mostly resistant. Mechano-phenotyping demonstrated that untreated AP-1060 cells were stiffer than untreated NB4 cells (Fig. 1A). After 4 days of 1 µM ATRA treatment only NB4 cells became more deformable (Fig. 1A). AP-1060 cells had limited maturation and no significant change in deformability. Recovery times were measured to report an apparent viscosity of the cells. AP-1060 cells were more viscous than NB4 cells (Fig. 1B). Treatment with ATRA significantly decreased the recovery time of AP-1060 cells, while there was no significant effect on NB4 cells. Overall, AP-1060 and NB4 cells had different responses to ATRA in both protein expression and mechanical phenotype, with ATRA having differential effects on elasticity (wCDI) and viscosity (recovery time).

APL cell responses to all-trans retinoic acid (ATRA).

Fig. 1. APL cell responses to all-trans retinoic acid (ATRA) (Brain L, Maslan A, et al., 2021).

Evaluating Sources of Technical Variability in the Mechano-Node-Pore Sensing Pipeline and Their Effect on the Reproducibility of Single-Cell Mechanical Phenotyping

Single-cell mechanical properties offer insights into cellular functions, and various microfluidics-based platforms have been developed for high-throughput testing. However, the technical variability and reproducibility of these platforms have not been fully characterized. Brain et al. evaluated the repeatability of mechano-node-pore sensing, a single-cell mechanical phenotyping platform, by assessing the impact of device-to-device variability and semi-manual data processing on measurement accuracy.

In node-pore sensing (NPS), a microfluidic channel is divided into wider "nodes" and narrower "pores." As cells are flowed through the device, characteristic current pulses are measured in a four-terminal configuration (Fig. 2A). The magnitude of these pulses is determined by the size of the cell and the transit time. In mechano-NPS, cells flow through several reference pores, a contraction segment, and recovery pores. The reference pores measure the cell's initial diameter and velocity, the contraction segment measures the cell's resistance to deformation, and the recovery pores measure the time taken to relax to the original size and shape. Each mechano-NPS device is optimized for a specific cell size. To evaluate the reproducibility, they re-used the same device designs from Kim et al. and Li et al. to measure MCF-10A and AP-1060 cells, respectively (Fig. 2B). The elastic properties of the cells are quantified with a whole-cell deformability index (wCDI), while the viscoelastic behavior is quantified with a recovery time. They quantified device-to-device variability and the impacts of data processing on the reproducibility by analyzing AP-1060 cells (Fig. 2C). They also examined the overall reproducibility in two labs using identical devices and MCF-10A cells.

Overview of mechano-node-pore sensing (mechano-NPS) operating principles, device design, and data processing pipeline.

Fig. 2. Overview of mechano-node-pore sensing (mechano-NPS) operating principles, device design, and data processing pipeline (Brain L, Cotner K L, et al., 2021).
What is the difference between clonal and subclonal?

Clonal mutations are shared by all cancer cells, whereas subclonal mutations are present only in a subset.

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Promising results

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29 Jan 2023


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