M3/M3v acute non lymphocytic leukemia (M3-ANLL) - M3/M3v acute myeloid leukemia (AML M3/M3v) - Acute promyelocytic leukemia (APL)

Some subtypes of acute myeloid leukemia (AML) share morphologic, immunophenotypic, and clinical features of acute promyelocytic leukemia (APL), but lack a PML–RARA (promyelocytic leukemia–retinoic acid receptor alpha) fusion gene. Instead, they have the retinoic acid receptor beta (RARB) or retinoic acid receptor gamma (RARG) rearranged. Almost all of these AML subtypes exhibit resistance to all-trans retinoic acid (ATRA); undoubtedly, the prognosis is poor. Here, we present an AML patient resembling APL with a novel cleavage and polyadenylation specific factor 6 ( CPSF6) –RARG fusion, showing resistance to ATRA and poor response to chemotherapy with homoharringtonine and cytarabine. Simultaneously, the patient also had extramedullary infiltration.

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Acute myeloid leukemia with mutated NPM1 mimics acute promyelocytic leukemia presentation

International Journal of Laboratory Hematology ◽

10.1111/ijlh.13357 ◽

2020 ◽

Author(s):

Manuel J. Arana Rosainz ◽

Nghia Nguyen ◽

Amer Wahed ◽

Laura C. Lelenwa ◽

Nfn Aakash ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Promyelocytic Leukemia ◽

Myeloid Leukemia ◽

Promyelocytic Leukemia ◽

Acute Myeloid

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ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression

Blood ◽

10.1182/blood-2005-07-3068 ◽

2006 ◽

Vol 107 (8) ◽

pp. 3330-3338 ◽

Cited By ~ 139

Author(s):

Beatrice U. Mueller ◽

Thomas Pabst ◽

José Fos ◽

Vibor Petkovic ◽

Martin F. Fey ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Retinoic Acid ◽

Acute Promyelocytic Leukemia ◽

Myeloid Leukemia ◽

Retinoic Acid Receptor ◽

Promyelocytic Leukemia ◽

All Trans Retinoic Acid ◽

Conditional Expression ◽

Neutrophil Differentiation ◽

Acute Myeloid

Abstract Tightly regulated expression of the transcription factor PU.1 is crucial for normal hematopoiesis. PU.1 knockdown mice develop acute myeloid leukemia (AML), and PU.1 mutations have been observed in some populations of patients with AML. Here we found that conditional expression of promyelocytic leukemia-retinoic acid receptor α (PML-RARA), the protein encoded by the t(15;17) translocation found in acute promyelocytic leukemia (APL), suppressed PU.1 expression, while treatment of APL cell lines and primary cells with all-trans retinoic acid (ATRA) restored PU.1 expression and induced neutrophil differentiation. ATRA-induced activation was mediated by a region in the PU.1 promoter to which CEBPB and OCT-1 binding were induced. Finally, conditional expression of PU.1 in human APL cells was sufficient to trigger neutrophil differentiation, whereas reduction of PU.1 by small interfering RNA (siRNA) blocked ATRA-induced neutrophil differentiation. This is the first report to show that PU.1 is suppressed in acute promyelocytic leukemia, and that ATRA restores PU.1 expression in cells harboring t(15;17).

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Comment on Geoffroy, M.-C.; de Thé H. Classic and Variants APLs, as Viewed from a Therapy Response. Cancers 2020, 12, 967

Cancers ◽

10.3390/cancers13235883 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5883

Author(s):

Zhan Su ◽

Xin Liu

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Promyelocytic Leukemia ◽

Myeloid Leukemia ◽

Therapy Response ◽

Promyelocytic Leukemia ◽

Acute Myeloid

Acute promyelocytic leukemia (APL) is a unique and very deeply studied acute myeloid leukemia [...]

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Acute Myeloid Leukemia and Acute Promyelocytic Leukemia

Hematology ◽

10.1182/asheducation-2003.1.82 ◽

2003 ◽

Vol 2003 (1) ◽

pp. 82-101 ◽

Cited By ~ 54

Author(s):

Bob Löwenberg ◽

James D. Griffin ◽

Martin S. Tallman

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Promyelocytic Leukemia ◽

Tyrosine Kinases ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Treatment Strategies ◽

Promyelocytic Leukemia ◽

Remission Induction ◽

Novel Drugs ◽

Acute Myeloid

Abstract The therapeutic approach to the patient with acute myeloid leukemia (AML) currently evolves toward new frontiers. This is particularly apparent from the entree of high-throughput diagnostic technologies and the identification of prognostic and therapeutic targets, the introduction of therapies in genetically defined subgroups of AML, as well as the influx of investigational approaches and novel drugs into the pipeline of clinical trials that target pathogenetic mechanisms of the disease. In Section I, Dr. Bob Löwenberg reviews current issues in the clinical practice of the management of adults with AML, including those of older age. Dr. Löwenberg describes upcoming possibilities for predicting prognosis in defined subsets by molecular markers and reviews experimental strategies to improve remission induction and postinduction treatment. In Section II, Dr. James Griffin reviews the mechanisms that lead to activation of tyrosine kinases by mutations in AML, the consequences of that activation for the cell, and the opportunities for targeted therapy and discusses some examples of developing novel drugs (tyrosine kinase inhibitors) and their effectiveness in AML (FLT3). In Section III, Dr. Martin Tallman describes the evaluation and management of patients with acute promyelocytic leukemia, a notable example of therapeutic progress in a molecularly defined entity of leukemia. Dr. Tallman focuses on the molecular genetics of APL, current curative treatment strategies and approaches for patients with relapsed and refractory disease. In addition, areas of controversy regarding treatment are addressed.

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Acute promyelocytic leukemia: preventing early complications and late toxicities

Hematology ◽

10.1182/asheducation-2016.1.10 ◽

2016 ◽

Vol 2016 (1) ◽

pp. 10-15 ◽

Cited By ~ 20

Author(s):

Sameem Abedin ◽

Jessica K. Altman

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Promyelocytic Leukemia ◽

Myeloid Leukemia ◽

Early Death ◽

Promyelocytic Leukemia ◽

Early Complications ◽

Younger Patients ◽

Success Stories ◽

Acute Myeloid

Abstract Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Therapeutic advances have made APL one of the true success stories in oncology, transforming this once lethal disease into the most curable form of AML. For many patients, cure will now be achieved without the use of chemotherapy. It is hoped that limiting chemotherapy will reduce mortality even further, particularly among more vulnerable older adults whose survival lagged behind that of younger patients. It should be noted that early death persists in patients with APL and continues to negatively affect survival. Further, among survivors treated with chemotherapy or even arsenic trioxide (ATO), there remains the potential for long-term toxicities that must be monitored. Understanding the management of these issues is an important complement to ensure maximal survival for patients with APL.

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Occurrence of myelodysplasia/acute myeloid leukemia 'on therapy' in two patients with acute promyelocytic leukemia

Indian Journal of Cancer ◽

10.4103/0019-509x.180843 ◽

2016 ◽

Vol 53 (1) ◽

pp. 59 ◽

Cited By ~ 2

Author(s):

X Thomas ◽

Y Chelghoum ◽

A Plesa ◽

S Ducastelle ◽

M Elhamri

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Promyelocytic Leukemia ◽

Myeloid Leukemia ◽

Promyelocytic Leukemia ◽

Acute Myeloid

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ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemia

Haematologica ◽

10.3324/haematol.2019.230482 ◽

2019 ◽

Vol 105 (9) ◽

pp. 2286-2297 ◽

Cited By ~ 4

Author(s):

Jianbiao Zhou ◽

Jessie Yiying Quah ◽

Yvonne Ng ◽

Jing-Yuan Chooi ◽

Sabrina Hui-Min Toh ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Promyelocytic Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Leukemia Cell ◽

Promyelocytic Leukemia ◽

Dihydroorotate Dehydrogenase ◽

Isocitrate Dehydrogenase 1 ◽

Pyrimidine Synthesis ◽

Acute Myeloid

Differentiation therapies achieve remarkable success in acute promyelocytic leukemia, a subtype of acute myeloid leukemia. However, excluding acute promyelocytic leukemia, clinical benefits of differentiation therapies are negligible in acute myeloid leukemia except for mutant isocitrate dehydrogenase 1/2. Dihydroorotate dehydrogenase catalyses the fourth step of the de novo pyrimidine synthesis pathway. ASLAN003 is a highly potent dihydroorotate dehydrogenase inhibitor that induces differentiation, as well as reduces cell proliferation and viability, of acute myeloid leukemia cell lines and primary acute myeloid leukemia blasts including in chemo-resistant cells. Apoptotic pathways are triggered by ASLAN003, and it also significantly inhibits protein synthesis and activates AP-1 transcription, contributing to its differentiation promoting capacity. Finally, ASLAN003 substantially reduces leukemic burden and prolongs survival in acute myeloid leukemia xenograft mice and acute myeloid leukemia patient-derived xenograft models. Notably, the drug has no evident effect on normal hematopoietic cells and exhibits excellent safety profiles in mice, even after a prolonged period of administration. Our results, therefore, suggest that ASLAN003 is an agent targeting dihydroorotate dehydrogenase with potential in the treatment of acute myeloid leukemia. ASLAN003 is currently being evaluated in phase 2a clinical trial in acute myeloid leukemia patients.

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