» Articles » PMID: 26110819

Establishment and Characterization of PCL12, a Novel CD5+ Chronic Lymphocytic Leukaemia Cell Line

Abstract

Immortalized cell lines representative of chronic lymphocytic leukemia (CLL) can assist in understanding disease pathogenesis and testing new therapeutic agents. At present, very few representative cell lines are available. We here describe the characterization of a new cell line (PCL12) that grew spontaneously from the peripheral blood (PB) of a CLL patient with progressive disease and EBV infection. The CLL cell origin of PCL12 was confirmed after the alignment of its IGH sequence against the "original" clonotypic sequence. The IGH gene rearrangement was truly unmutated and no CLL-related cytogenetic or genetic lesions were detected. PCL12 cells express CD19, CD20, CD5, CD23, low levels of IgM and IgD and the poor-outcome-associated prognostic markers CD38, ZAP70 and TCL1. In accordance with its aggressive phenotype the cell line is inactive in terms of LYN and HS1 phosphorylation. BcR signalling pathway is constitutively active and anergic in terms of p-ERK and Calcium flux response to α-IgM stimulation. PCL12 cells strongly migrate in vitro in response to SDF-1 and form clusters. Finally, they grow rapidly and localize in all lymphoid organs when xenotrasplanted in Rag2-/-γc-/- mice. PCL12 represents a suitable preclinical model for testing pharmacological agents.

Citing Articles

culture of leukemic cells in collagen scaffolds and carboxymethyl cellulose-polyethylene glycol gel.

Svozilova H, Vojtova L, Matulova J, Bruknerova J, Polakova V, Radova L PeerJ. 2024; 12:e18637.

PMID: 39655330 PMC: 11627079. DOI: 10.7717/peerj.18637.


CD38 regulates chronic lymphocytic leukemia proliferation via CD45 phosphatase activity.

Imbery J, Wiik C, Heinzelbecker J, Jebsen J, Dobbing M, Bottini N Mol Ther Oncol. 2024; 32(3):200841.

PMID: 39474602 PMC: 11519781. DOI: 10.1016/j.omton.2024.200841.


Cyclic Fasting-Mimicking Diet Plus Bortezomib and Rituximab Is an Effective Treatment for Chronic Lymphocytic Leukemia.

Raucci F, Vernieri C, Di Tano M, Ligorio F, Blazevits O, Lazzeri S Cancer Res. 2024; 84(7):1133-1148.

PMID: 38241703 PMC: 10982641. DOI: 10.1158/0008-5472.CAN-23-0295.


Toll-like receptor 9 signaling in chronic lymphocytic leukemia cell lines.

Meloni M, Sana I, Mantione M, Riba M, Muzio M FEBS Open Bio. 2023; 13(12):2367-2374.

PMID: 37881888 PMC: 10699106. DOI: 10.1002/2211-5463.13726.


Effects of blocking CD24 and CD47 'don't eat me' signals in combination with rituximab in mantle-cell lymphoma and chronic lymphocytic leukaemia.

Aroldi A, Mauri M, Ramazzotti D, Villa M, Malighetti F, Crippa V J Cell Mol Med. 2023; 27(20):3053-3064.

PMID: 37654003 PMC: 10568669. DOI: 10.1111/jcmm.17868.


References
1.
Zenz T, Mertens D, Kuppers R, Dohner H, Stilgenbauer S . From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer. 2009; 10(1):37-50. DOI: 10.1038/nrc2764. View

2.
Rasul E, Salamon D, Nagy N, Leveau B, Banati F, Szenthe K . The MEC1 and MEC2 lines represent two CLL subclones in different stages of progression towards prolymphocytic leukemia. PLoS One. 2014; 9(8):e106008. PMC: 4146575. DOI: 10.1371/journal.pone.0106008. View

3.
Mockridge C, Potter K, Wheatley I, Neville L, Packham G, Stevenson F . Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status. Blood. 2007; 109(10):4424-31. DOI: 10.1182/blood-2006-11-056648. View

4.
Stacchini A, Aragno M, Vallario A, Alfarano A, Circosta P, Gottardi D . MEC1 and MEC2: two new cell lines derived from B-chronic lymphocytic leukaemia in prolymphocytoid transformation. Leuk Res. 1999; 23(2):127-36. DOI: 10.1016/s0145-2126(98)00154-4. View

5.
Lanemo Myhrinder A, Hellqvist E, Bergh A, Jansson M, Nilsson K, Hultman P . Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia. Leuk Lymphoma. 2013; 54(8):1769-79. DOI: 10.3109/10428194.2013.764418. View