Although the majority of patients with acute promyelocytic leukemia (APL) are potentially cured by treatments combining all-trans retinoic acid (ATRA) and chemotherapy (CHT), a sizable proportion (around30%)will relapseduring follow-up.Retrospective molecular monitoring studies using reverse transcriptasepolymerase chain reaction (RT-PCR) for the specific PML/RARa fusion gene, have shown that a...

Fusion proteins present in leukemic cells frequently contain a new amino acid at the fusion point. We tested whether a peptide (BCR1/25) encompassing the fusion region of the hybrid molecule pml/RARa, which is selectively expressed by acute promyelocytic leukemia (APL) cells, can be recognized by human T lymphocytes in vitro. CD4+ lymphocytes, at both polyclonal and clonal level, recognized pep...

1 Bone marrow aspirate and trephine biopsy unless the peripheral blast count is high. 2 Immunophenotyping [CD3, CD7, CD13, CD14, CD33, CD34, CD64, CD117 and cytoplasmic myeloperoxidase (MPO)]. 3 Cytochemistry (MPO or Sudan Black, combined esterase). Can be omitted if four-colour flow cytometry is available. 4 Cytogenetics [with reverse-transcription polymerase chain reaction (RT-PCR) for AML 1-...

The ret finger protein (rfp) is a member of the B-box zinc finger gene family many of which may function in growth regulation and in the appropriate context become oncogenic. Members of this family are nuclear proteins that possess a characteristic tripartite motif consisting of the RING and B-box zinc binding domains and a coiled-coil domain. The promyelocytic leukemia gene (PML), another B-bo...

The hierarchical level of stem cell involvement in acute promyelocytic leukemia (APL) characterized by the pathognomonic PML-RARA fusion gene is unknown. To determine if the cells of the primitive hematopoietic stem cell compartment are involved in the leukemic process, we have used molecular and cell sorting techniques in peripheral blood and bone marrow (BM) cells at diagnosis from three pati...

Arsenic trioxide (As₂O₃) is a highly effective treatment for patients with refractory/relapsed acute promyelocytic leukemia (APL), but resistance to As₂O₃ has recently been seen. In the present study, we report the findings that 2 of 15 patients with refractory/relapsed APL treated with As₂O₃ were clinically As₂O₃ resistant. Leukemia cells from these 2 patients harbored missense mutations in pr...

The role of fusion proteins in acute myeloid leukemia (AML) is well recognized, but the leukemic target cell and the cellular mechanisms generating the AML phenotype are essentially unknown. To address this issue, an in vitro model to study the biologic activity of leukemogenic proteins was established. Highly purified human hematopoietic progenitor cells/stem cells (HPC/HSC) in bulk cells or s...

RETINOIDS AND IN particular retinoic acid are naturally occurring compounds that regulate the growth and differentiation of a variety of different cell types. The observation that retinoic acid induces the terminal differentiation of human acute promyelocytic leukemia (APL) cells both in vitro1 and in vivo2-4 has had a significant impact in clinical hematology and has altered our approach to th...

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolys...