Classic and Variants APLs, as Viewed from a Therapy Response

Geoffroy, M

doi:10.3390/cancers12040967

Cited by 41 publications

(48 citation statements)

References 173 publications

(210 reference statements)

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“…As aforementioned, the classical hallmark of APL is the cytogenetic translocation t(15;17), present in 95–98% of cases, and detectable by the specific fluorescence in situ hybridization (FISH) probes, and more rapid molecular biology techniques such as reverse transcriptase polymerase chain reaction (RT-PCR). However, a small percentage of cases presents different RARA fusion partners, such as nucleophosmin (NPM1, 5q35), signal transducer, and activator of transcription (STAT5B, 17q21), factor interacting with PAPOLA and CPSF1 (FIP1L1, 4q12), promyelocytic leukemia zinc finger (PLZF, now known as ZBTB16, 11q23) and nuclear matrix-mitotic apparatus protein 1 (NUMA1, 11q13) [ 22 , 23 , 24 , 25 , 26 ]. These rare cases of “APL variant” are characterized by the same clinical picture of classic APL but different sensitivity to ATRA/ATO combination [ 27 , 28 ] ( Table 1 ).…”

Section: Diagnostics Clinical Features and Risk Assessmentmentioning

confidence: 99%

Acute Promyelocytic Leukemia in Children: A Model of Precision Medicine and Chemotherapy-Free Therapy

Gurnari

Voso

Girardi

et al. 2021

IJMS

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Acute promyelocytic leukemia (APL) represents a paradigm of precision medicine. Indeed, in the last decades, the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) completely revolutionized the therapeutic approach to this previously highly fatal disorder. This entirely chemotherapy-free treatment, which provided excellent survival rates, has been initially validated in adults and, recently, translated in the pediatric setting. This review summarizes currently available data on the use of ATRA and ATO combination in pediatric APL, providing a particular focus on peculiar issues and challenges, such as the occurrence of pseudotumor cerebri and death during induction (early death), as well as the advantage offered by the ATO/ATRA combination in sparing long-term sequelae.

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Section: Diagnostics Clinical Features and Risk Assessmentmentioning

confidence: 99%

Acute Promyelocytic Leukemia in Children: A Model of Precision Medicine and Chemotherapy-Free Therapy

Gurnari

Voso

Girardi

et al. 2021

IJMS

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“…The underlying molecular mechanisms of clinical resistance to RA and/or ATO are not all well-known in different X-RARA fusion proteins [ 65 ]. Interestingly, other rare variant APL fusion proteins do not involve RARA, but other RAR receptors, such as RA receptor beta (RARB) and RA receptor gamma (RARG) [ 66 ].…”

Section: Ra and Annexins In Myelopoiesis And Acute Promyelocytic Lmentioning

confidence: 99%

Emerging Cancer Epigenetic Mechanisms Regulated by All-Trans Retinoic Acid

Rossetti

Sacchi

2020

Cancers

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All-trans retinoic acid (RA), which is the dietary bioactive derivative obtained from animal (retinol) and plant sources (beta-carotene), is a physiological lipid signal of both embryonic and postembryonic development. During pregnancy, either RA deficiency or an excessive RA intake is teratogenic. Too low or too high RA affects not only prenatal, but also postnatal, developmental processes such as myelopoiesis and mammary gland morphogenesis. In this review, we mostly focus on emerging RA-regulated epigenetic mechanisms involving RA receptor alpha (RARA) and Annexin A8 (ANXA8), which is a member of the Annexin family, as well as ANXA8 regulatory microRNAs (miRNAs). The first cancer showing ANXA8 upregulation was reported in acute promyelocytic leukemia (APL), which induces the differentiation arrest of promyelocytes due to defective RA signaling caused by RARA fusion genes as the PML-RARA gene. Over the years, ANXA8 has also been found to be upregulated in other cancers, even in the absence of RARA fusion genes. Mechanistic studies on human mammary cells and mammary glands of mice showed that ANXA8 upregulation is caused by genetic mutations affecting RARA functions. Although not all of the underlying mechanisms of ANXA8 upregulation have been elucidated, the interdependence of RA-RARA and ANXA8 seems to play a relevant role in some normal and tumorigenic settings.

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“…2,3 Fourteen variant translocations involving the RARA gene have been described: ZBTB16-RARA, NPM-RARA, NuMA-RARA, STAT5B-RARA, PRKAR1A-RARA, BCOR-RARA, FIP1L1-RARA, OBFC2A-RARA, GTF2I-RARA, IRF2BP2-RARA, FNDC3B-RARA, STAT3-RARA, TBLR1-RARA, and TGF-RARA. 8 Among these, the ZBTB16-RARA fusion, previously known as PLZF-RARA, results from the reciprocal translocation between ZBTB16 (zinc finger and BTB domain containing 16) on chromosome 11, and the RARA gene on chromosome 17 [t(11;17)(q23;q21)]. This is the most frequently reported variant, accounting for about 1% of all APL-like AML.…”

Section: Introductionmentioning

confidence: 99%