The unique t(15;17) of acute promyelocytic leukemia (APL) retinoid response elements (RAREs). This leads to a dominant negative block of transcription from RAREs that is dosefuses the PML gene with the retinoic acid receptor a (RARa) gene. Although retinoic acid (RA) inhibits cell growth and dependent and not relieved by RA. An unrearranged RARa engineered with this mutation also lost ligand bi...

The unique t(15;17) of acute promyelocytic leukemia (APL) retinoid response elements (RAREs). This leads to a dominant negative block of transcription from RAREs that is dosefuses the PML gene with the retinoic acid receptor a (RARa) gene. Although retinoic acid (RA) inhibits cell growth and dependent and not relieved by RA. An unrearranged RARa engineered with this mutation also lost ligand bi...

Tumor-associated chromosome translocations usually lead to the formation of two reciprocal fusion genes: one thought to be involved in the transformation process, the other the mechanical consequence of the translocation event. In the case of acute promyelocytic leukemia (APL) blasts, the 15;17 chromosome translocation generates the putatively transforming PML/RARa fusion gene and its reciproca...

The diagnosis of acute promyelocytic leukaemia (APL) is usually confirmed by cytogenetics showing the characteristic t(15;17), but a minority of patients have a masked PML/RARA fusion. We report ten patients with APL and no evidence of the t(15;17), in whom the insertion of RARA into PML could not be demonstrated by initial FISH studies using a standard dual fusion probe but was readily identif...

Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over seven different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require a combination of advanced cytogenetic and molecular techniques for accurate characterizatio...

A total of 97 acute promyelocytic leukemia (APL) patients with adequate flow cytometry (FC) data, bone marrow aspirates and presence of t(15;17)/PML-RARA by cytogenetics and/or FISH studies were analyzed for immunophenotypic pattern. Leukemic cells had the following phenotype: CD11b-, CD11c-, CD13+, CD33+, CD45+, CD64+/-, CD117+, and HLA-DR-. A subset of cases showed also an expression of CD2, ...

Acute promyelocytic leukemia (APL) is associated with a chromosomal translocation t(15;17) and successfully differentiated by all-trans-retinoic acid (ATRA) in vivo as well as in vitro. The PML-retinoic acid receptor alpha (RARA) oncoprotein, which is generated by the translocation, blocks the differentiation, and ATRA is thought to modulate the dominant negative function of PML-RARA. However, ...

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations always involving the RARa gene, which variably fuses to one of several distinct loci, including PML or PLZF (X genes) in t(15;17) or t(11;17), respectively. APL in patients harboring t(15;17) responds well to retinoic acid (RA) treatment and chemotherapy, whereas t(11;17) APL responds poorly to both treatments, thu...

Acute promyelocytic leukemia (APL) is characterized by the PML-RARA fusion gene. To identify genetic changes that cooperate with PML-RARA, we performed spectral karyotyping analysis of myeloid leukemias from transgenic PML-RARA mice and from mice coexpressing PML-RARA and BCL2, IL3, activated IL3R, or activated FLT3. A cooperating mutation that enhanced survival (BCL2) was not sufficient to com...

Acute promyelocytic leukemia (APL) is characterized by the t(15;17) translocation that generates the fusion protein promyelocytic leukemia-retinoic acid receptor α (PML-RARA) in nearly all cases. Multiple prior mouse models of APL constitutively express PML-RARA from a variety of non-Pml loci. Typically, all animals develop a myeloproliferative disease, followed by leukemia in a subset of anima...