Asynchronous expression of myeloid antigens in leukemic cells in a PML/RARalpha transgenic mouse model

Abstract

Acute promyelocytic leukemia (APL) is characterized by the expansion of blasts that resemble morphologically promyelocytes and harbor a chromosomal translocation involving the retinoic acid receptor α (RARα) and the promyelocytic leukemia (PML) genes on chromosomes 17 and 15, respectively. The expression of the PML/ RARα fusion gene is essential for APL genesis. In fact, transgenic mice (TM) expressing PML/RARα develop a form of leukemia that mimics the hematological findings of human APL. Leukemia is diagnosed after a long latency (approximately 12 months) during which no hematological abnormality is detected in peripheral blood (pre-leukemic phase). In humans, immunophenotypic analysis of APL blasts revealed distinct features; however, the precise immunophenotype of leukemic cells in the TM model has not been established. Our aim was to characterize the expression of myeloid antigens by leukemic cells from hCG-PML/RARα TM. In this study, TM (N = 12) developed leukemia at the mean age of 13.1 months. Morphological analysis of bone marrow revealed an increase of the percentage of immature myeloid cells in leukemic TM compared to pre-leukemic TM and wild-type controls (48.63 ± 16.68, 10.83 ± 8.11, 7.4 ± 5.46%, respectively; P < 0.05). Flow cytometry analysis of bone marrow and spleen from leukemic TM identified the asynchronous co-expression of CD34, CD117, and CD11b. This abnormal phenotype was rarely detected prior to the diagnosis of leukemia and was present at similar frequencies in hematologically normal TM and wild-type controls of different ages. The present results demonstrate that, similarly to human APL, leukemic cells from hCG-PML/RARα TM present a specific immunophenotype.

(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1

“…2A). The CD34 marker represents leukaemia stem cells, typically observed in AML 29 ; the CD117 marker is the c-kit proto-oncogene encoding the receptor tyrosine kinase involved in the proliferation of leukaemia cells found in the stage one of myeloid differentiation 30 . EGCG treatment reduced the percentage of CD45 + CD34 + cells in the bone marrow (Fig.…”

“…Reductions of CD45 + CD34 + and/or CD45 + CD117 + cells were antigens 23,25 . The CD34 represents the leukaemia stem cells, typically observed in acute myeloid leukaemia 29 ; the CD117 is the c-kit proto-oncogene encoding the receptor tyrosine kinase involved in the proliferation of leukaemia cells found in stage one of myeloid differentiation 30 . EGCG treatment also increased the number of mature cells (CD11b + /Gr-1 + ) in bone marrow, and the number of circulating neutrophils and monocytes, suggesting that EGCG induced cell differentiation.…”

(+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo

“…The analysis was restricted to the myeloid marker CD117 þ cells, which is expressed by APL cells of the TM model. 26 Treatment with a-TOS significantly increased the mean number of apoptotic cells compared with control (65.1 vs 37.2%, P ¼ 0.007). Morphologic analysis confirmed this result ( Figure 6d) and similar results were obtained for leukemic cells infiltrating the liver (data not shown).…”

Methionine-induced hyperhomocysteinemia reverts fibrinolytic pathway activation in a murine model of acute promyelocytic leukemia

“…After 21 days, development of leukemia was assessed by morphology and by determining the percentage of CD117 ϩ cells in the BM by flow cytometry, as described previously. 21 All of the animals were killed by overdose of 2.5% tribromoethanol 21 days after the transplantation, and blood was collected from the inferior vena cava after infusion of 180 L of 3.2% sodium citrate, as described previously. 22 The samples were centrifuged and plasma was frozen at Ϫ80°C.…”