Myeloid leukemia differentiation by phorbol ester and retinoic acid: A practical approach

Abstract

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular recognition of acute myeloid leukemia using aptamers

“…Several studies have reported NB4 and HL60 differentiation pathways associated with ATRA and sodium butyrate induction 8, 9,10, 11, 12. We therefore used the nitroblue tetrazolium (NBT) reduction test to assess and confirm that the leukemic blasts differentiate into peroxidase-positive leukocytes (neutrophils and monocytes).…”

Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

“…The parental cell line used in the present study K562 cells as well as Lucena 1 cells are characterised by carrying foetal haemoglobin as defined by benzidine negative staining (Marques-Silva 1996). The use of the differentiating agents retinoic acid and phorbol ester, known to differentiate a number of leukaemic cells (Marques-Silva et al 1990), were incapable of leading these cells lines, K562 and Lucena 1, to switch to the synthesis of adult haemoglobin whereas the chemotherapic 5-fluorouracil not only produced the haemoglobin switch but induced the extrusion of Rho 123 from K562 cells and augmented the one seen in Lucena 1 cells (Fig. 5) (Marques-Silva 1996).…”

The SHP2‐ERK2 signaling pathway regulates branched I antigen formation by controlling the binding of CCAAT/enhancer binding protein α to the IGnTC promoter region during erythroid differentiation

“…To address this, we first established a K‐562 cell model as an alternative to primary CD34+ cells. K‐562 cells can be manipulated easily by SB and RA to differentiate into erythroid lineages and granulocytic lineages, respectively . To monitor differentiation status, we examined the expression of two differentiation markers, namely, Hb and CD15, using benzidine staining for Hb and fluorescence‐activated cell sorting (FACS) analysis for CD15 .…”