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Blood Reviews Mar 2015Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among... (Review)
Review
Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent-de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed.
Topics: Child; Cytogenetics; Environmental Exposure; Geography, Medical; Humans; Leukemia, Promyelocytic, Acute; Prognosis; Risk Factors
PubMed: 25445717
DOI: 10.1016/j.blre.2014.09.013 -
Oncotarget Aug 2013
Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Drug Resistance, Neoplasm; Humans; Leukemia, Promyelocytic, Acute; Molecular Targeted Therapy; Oxides; Tretinoin
PubMed: 23934744
DOI: 10.18632/oncotarget.1244 -
The Journal of International Medical... Dec 2022Internal tandem duplications of the Fms-like tyrosine kinase 3 gene ( and additional chromosomal abnormalities (ACA) are prognostic factors in patients with acute...
OBJECTIVES
Internal tandem duplications of the Fms-like tyrosine kinase 3 gene ( and additional chromosomal abnormalities (ACA) are prognostic factors in patients with acute promyelocytic leukemia (APL). This study aimed to determine the effect of the association between and ACA in the prognosis of APL.
METHODS
This was a retrospective cohort study including 60 patients with APL treated with all-trans retinoic acid (ATRA) and chemotherapy. Five-year overall survival (OS) and progression-free survival (PFS) were analyzed in patient groups according to the presence of and ACA.
RESULTS
was an independent adverse factor for 5-year PFS, and ACA was an independent adverse factor for 5-year OS. There were significant differences in OS and PFS among the groups: -negative without ACA, -positive without ACA, -negative with ACA, and -positive with ACA. The OS times were 52.917, 45.813, 25.375, and 23.417 months, and the PFS times were 48.833, 38.563, 23.250, and 17.333 months, respectively.
CONCLUSION
and ACA are associated with the poorest OS and PFS outcomes in patients with APL treated with chemotherapy plus ATRA.
Topics: Humans; Leukemia, Promyelocytic, Acute; Retrospective Studies; Mutation; Chromosome Aberrations; Prognosis; Tretinoin; Leukemia, Myeloid, Acute; fms-Like Tyrosine Kinase 3
PubMed: 36539954
DOI: 10.1177/03000605221138490 -
The Journal of Experimental Medicine Dec 2013Acute promyelocytic leukemia (APL) is a hematological malignancy driven by a chimeric oncoprotein containing the C terminus of the retinoic acid receptor-a (RARa) fused... (Review)
Review
Acute promyelocytic leukemia (APL) is a hematological malignancy driven by a chimeric oncoprotein containing the C terminus of the retinoic acid receptor-a (RARa) fused to an N-terminal partner, most commonly promyelocytic leukemia protein (PML). Mechanistically, PML-RARa acts as a transcriptional repressor of RARa and non-RARa target genes and antagonizes the formation and function of PML nuclear bodies that regulate numerous signaling pathways. The empirical discoveries that PML-RARa-associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Critically, the mechanistic insights gleaned from these studies have resulted not only in a better understanding of APL itself, but also carry valuable lessons for other malignancies.
Topics: Animals; Arsenic Trioxide; Arsenicals; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Gene Expression Regulation, Leukemic; Humans; Leukemia, Promyelocytic, Acute; Mice; Oncogene Proteins, Fusion; Oxides; Remission Induction; Signal Transduction; Transcriptional Activation; Tretinoin
PubMed: 24344243
DOI: 10.1084/jem.20131121 -
Tidsskrift For Den Norske Laegeforening... May 2014Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid leukaemia (AML) with unique biological and clinical features and unique therapeutic requirements. The... (Review)
Review
BACKGROUND
Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid leukaemia (AML) with unique biological and clinical features and unique therapeutic requirements. The article provides a brief description of the development, pathophysiology, diagnosis and treatment of APL.
METHOD
The article is based on the authors' own experience and reviews of key articles and national and international guidelines.
RESULTS
The disease is caused by a single genetic event, namely the translocation t(15;17), which gives rise to the oncoprotein PML-RARA. Clinical and morphological characteristics arouse suspicion of the disease, and the diagnosis is verified by detecting the translocation. At the time of diagnosis most patients have severe coagulopathy and the predominant clinical manifestation is bleeding. Early mortality is due to severe haemorrhage, usually intracranial. Early treatment start with all-trans retinoic acid (ATRA) on suspicion of APL is essential to reduce this early mortality. ATRA is also an important part of continued treatment, in combination with anthracycline-based chemotherapy and possibly arsenic. After this treatment, the prognosis for disease-free long-term survival is > 90%. There are also safe and effective treatment options for elderly patients with complex comorbidities.
INTERPRETATION
With APL it is particularly important to start disease-targeting therapy in the form of ATRA quickly because of the high risk of serious haemorrhages and high early mortality. If serious haemorrhages are avoided, the prognosis is very good.
Topics: Antineoplastic Agents; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Humans; Leukemia, Promyelocytic, Acute; Oncogene Proteins, Fusion; Translocation, Genetic; Tretinoin
PubMed: 24865730
DOI: 10.4045/tidsskr.13.1508 -
BMC Cancer Feb 2023The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance.
BACKGROUND
The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance.
METHODS
Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers.
RESULTS
APL occurred in 374 males and 387 females at a median age of 44 (1-97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 10/L, diagnosis during 1991-2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14-161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 10/L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010-2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens.
CONCLUSIONS
There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754).
Topics: Male; Female; Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Arsenic Trioxide; Leukemia, Promyelocytic, Acute; Neoplasms, Second Primary; Neoplasm Recurrence, Local; Tretinoin; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Oxides; Arsenicals
PubMed: 36765318
DOI: 10.1186/s12885-023-10612-z -
Experimental Cell Research May 2014Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate... (Review)
Review
Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.
Topics: Animals; Autophagy; Cell Differentiation; Hematopoiesis; Humans; Leukemia, Promyelocytic, Acute; Receptors, Retinoic Acid; Retinoids; Signal Transduction
PubMed: 24694321
DOI: 10.1016/j.yexcr.2014.03.018 -
Leukemia & Lymphoma Aug 2021Acute promyelocytic leukemia (APL) boasts overall survival (OS) of >90% at 3 years and early mortality of <5% in recent clinical trials. Using a large National Cancer...
Acute promyelocytic leukemia (APL) boasts overall survival (OS) of >90% at 3 years and early mortality of <5% in recent clinical trials. Using a large National Cancer Database, we performed analysis of 7190 adults with APL to determine whether one-month mortality and OS of patients with APL treated in real-world practices mirror outcomes noted in clinical trials. Only 64% of total patients received multi-agent therapy; 32% received either single-agent therapy or no therapy at all. One-month mortality was 6% for patients ≤18 years, 6% for 19-40 years, 10% for 41-60 years, and 21% for >60 years. OS at 1- and 3-year were 81% and 75%, respectively. In a multivariate analysis, age ≤ 40 years, treatment at academic center, use of multi-agent therapy, and diagnosis after 2009 conferred better OS. In this largest database study in APL till date, we demonstrated an overall improvement in OS over time but challenges still exist in translating successes of clinical trials to real-world practices.
Topics: Adult; Clinical Trials as Topic; Humans; Leukemia, Promyelocytic, Acute
PubMed: 33711907
DOI: 10.1080/10428194.2021.1894651 -
Blood Oct 1993
Review
Topics: Drug Resistance; Humans; Leukemia, Promyelocytic, Acute; Retinoids; Tretinoin; Tumor Cells, Cultured
PubMed: 8400247
DOI: No ID Found -
Annals of Hematology Feb 2024The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We...
The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.
Topics: Humans; Adult; Leukemia, Promyelocytic, Acute; Tretinoin; Neoplasms, Second Primary; Incidence; Retrospective Studies; Treatment Outcome; Risk Factors; Pathologic Complete Response; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38110588
DOI: 10.1007/s00277-023-05582-y