Acute promyelocytic leukemia (APL) is always associated with chromosomal translocations that disrupt the retinoic acid receptor a (RARa) gene. Whether these translocations relate to a role for endogenous RARa in normal granulopoiesis remains uncertain because most studies addressing this question have used nonphysiological overexpression systems. Granulocyte differentiation in cells derived fro...

Acute promyelocytic leukemia (APL) cells, containing the t(15;17) rearrangement, express the fusion protein, PML/ RARa. Clinically, patients respond to all-trans retinoic acid (ATRA) through complete remissions associated with myeloid maturation of leukemic cells. This clinical ATRA response of APL is linked to PML/RARa expression. Unfortunately, these remissions are transient and relapsed APL ...

PML/RARA, a potent transcriptional inhibitor of nuclear receptor signaling, represses myeloid differentiation genes and drives acute promyelocytic leukemia (APL). Association of the retinoid X receptor-α (RXRA) coreceptor to PML/RARA is required for transformation, with RXRA promoting its efficient DNA binding. APL is exquisitely sensitive to retinoic acid (RA) and arsenic trioxide (arsenic), w...

Because PML-RARA-induced acute promyelocytic leukemia (APL) is a morphologically differentiated leukemia, many groups have speculated about whether its leukemic cell of origin is a committed myeloid precursor (e.g. a promyelocyte) versus an hematopoietic stem/progenitor cell (HSPC). We originally targeted PML-RARA expression with CTSG regulatory elements, based on the early observation that thi...

Signal transducer and activator of transcription (STAT) 5b-retinoic acid receptor (RAR) a is the fifth fusion protein identified in acute promyelocytic leukemia (APL). Initially described in a patient with all-trans retinoic acid (ATRA)–unresponsive disease, STAT5b-RARa resulted from an interstitial deletion on chromosome 17. To determine the molecular mechanisms of myeloid leukemogenesis and m...

The majority of acute promyelocytic leukemia (APL) cases are characterized by the presence of a promyelocytic leukemia-retinoic acid receptor alpha(RARA) fusion gene. In a small subset, RARA is fused to a different partner, usually involved in regulating cell growth and differentiation. Here, we identified a novel RARA fusion transcript, BCOR-RARA, in a t(X;17)(p11;q12) variant of APL with uniq...

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...

PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colo...

The PML gene is frequently fused to the retinoic acid receptor a (RARa) gene in acute promyelocytic leukemia (APL), generating a characteristic PML-RARa oncogenic chimera. PML-RARa disrupts the discrete nuclear speckles termed nuclear bodies, which are formed in PML, suggesting that nuclear body disruption is involved in leukemogenesis. Nuclear body formation that relies upon PML oligomerizatio...