NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3)

Abstract

Acute promyelocytic leukemia (APL) is a well-defined entity among acute leukemia, cytogenetically characterized by a t(15;17) (q22;q11–12) translocation. In vitro and in vivo studies suggest that all-trans retinoic acid (RA) treatment restores cell maturation. We have isolated the first permanent cell line with t(15;17), derived from the marrow of a patient with APL in relapse. The establishment of the cell line, its morphologic, karyotypic, and immunohistochemical features are reported. RA induced cell line maturation. Cells strongly expressed myeloid markers, but also some T-cell markers. Additional karyotypic abnormalities, a 12p rearrangement and the possible presence of a homogeneous staining region (HSR) on 19q+ are discussed both in relation to T-cell (CD2, CD4) and monocyte (CD9) markers, and to the acquired cell growth autonomy. The cell line represents a remarkable tool for biomolecular studies.

Identification of a novel and myeloid specific role of the leukemia‐associated fusion protein DEK‐NUP214 leading to increased protein synthesis

“…The human myeloid cell lines HL‐60 (Collins et al, 1977), NB4 (Lanotte et al, 1991), U‐937 (Sundstrom and Nilsson, 1976), and K562 (Lozzio and Lozzio, 1975), the human T cell leukemia cell line Molt‐4, and the human NK/T leukemia cell line YT‐indy were grown in RPMI 1640 culture medium supplemented with 10% heat‐inactivated FCS (FCS). The human embryonic kidney cell line 293T/17 and the epithelial cell line HeLa were grown in DMEM (DMEM) containing 10% FCS plus penicillin and streptomycin.…”

Extracellular ATP couples to cAMP generation and granulocytic differentiation in human NB4 promyelocytic leukaemia cells

“…NB4 is a relatively newly created promyelocytic leukaemia cell line established from a patient with acute promyelocytic leukaemia (APL; FAB classification, M3) 1 . Unlike HL‐60 cells, NB4 cells contain the clinically relevant t(15;17) translocation unique to APL patients 1 and present in 90% of these patients. This translocation creates a hybrid gene between the C‐terminus of the retinoic acid receptor‐α (RARα) and the N‐terminus of the promyelocytic leukaemia (PML) locus, resulting in a PML‐RARα fusion gene.…”

“…All‐ trans retinoic acid (ATRA) has been shown to play a role in granulocytic maturation, in particular in HL‐60 and NB4 cells 1 , 4 . In addition, the administration of ATRA has been used to treat patients with APL, 5 believed to be through ATRA‐induced differentiation of the leukaemic cells 6 .…”

Wogonin induces the granulocytic differentiation of human NB4 promyelocytic leukemia cells and up‐regulates phospholipid scramblase 1 gene expression

“…The NB4 cell line carried the t(15;17) translocation resulting in the joining of the promyelocytic leukemia‐associated protein (PML) oncogene to the gene encoding the retinoic acid receptor‐α (RARα). ( 13,14 ) It has been shown that the fusion gene plays a central role in leukemogenesis in APL and the presence of the PML/RARα fusion protein disrupts the normal location of the PML nuclear body and interferes with the function of PML for growth inhibition. ( 14 ) Previous studies have also demonstrated that NB4 cell line could be differentiated along granulocytic or monocyte/macrophage pathway by various differentiation inducers, providing an excellent model for studying cell differentiation.…”