Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Management of Acute Promyelocytic Leukemia at Extremes of Age.

ABSTRACT: Tailored treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal disease to one of the most curable malignant diseases in humans. Due to its high efficacy, ATO/ATRA is the standard first-line therapy in younger adult, non-high-risk APL patients. However, early death is still a major issue in APL, particularly in older patients. Thus, rapid diagnostics, immediate access to ATRA-based therapy, and supportive care are of utmost importance. Nevertheless, challenging situations occur, particularly in patients excluded from controlled studies with clinical knowledge mainly based on case reports and registries. Besides the treatment of newly diagnosed patients, managing toxicities and complications remains challenging. This review discusses the approach to the treatment of APL in elderly and pediatric patients.

SUBMITTER: Kayser S

PROVIDER: S-EPMC10377629 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Management of Acute Promyelocytic Leukemia at Extremes of Age.

Kayser Sabine S Conneely Shannon E SE

Cancers 20230715 14

Tailored treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal disease to one of the most curable malignant diseases in humans. Due to its high efficacy, ATO/ATRA is the standard first-line therapy in younger adult, non-high-risk APL patients. However, early death is still a major issue in APL, particularly in older patients. Thus, rapid diagnostics, immediate access to ATRA-based thera ...[more]

PMID: 37509298

Similar Datasets

History of Acute Promyelocytic Leukemia.

Project description:In this article, we discuss the history of acute promyelocytic leukemia (APL) from the pre-therapeutic era, which began after its recognition by Hillestad in 1947 as a nosological entity, to the present day. It is a paradigmatic history that has transformed the "most malignant leukemia form" into the most curable one. The identification of a balanced reciprocal translocation between chromosomes 15 and 17, resulting in fusion between the promyelocytic leukemia gene and the retinoic acid receptor alpha, has been crucial in understanding the mechanisms of leukemogenesis, and responsible for the peculiar response to targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). We review the milestones that marked successive therapeutic advances, beginning with the introduction of the first successful chemotherapy in the early 1970s, followed by a subsequent incorporation of ATRA and ATO in the late 1980s and early 1990s which have revolutionized the treatment of this disease. Over the past two decades, treatment optimization has relied on the combination of ATRA, ATO, and chemotherapy according to risk-adapted approaches, which together with improvements in supportive therapy have paved the way for cure for most patients with APL.

| S-EPMC8690702 | biostudies-literature

Current views on the genetic landscape and management of variant acute promyelocytic leukemia.

Project description:Acute promyelocytic leukemia (APL) is characterized by the accumulation of promyelocytes in bone marrow. More than 95% of patients with this disease belong to typical APL, which express PML-RARA and are sensitive to differentiation induction therapy containing all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), and they exhibit an excellent clinical outcome. Compared to typical APL, variant APL showed quite different aspects, and how to recognize, diagnose, and treat variant APL remained still challenged at present. Herein, we drew the genetic landscape of variant APL according to recent progresses, then discussed how they contributed to generate APL, and further shared our clinical experiences about variant APL treatment. In practice, when APL phenotype was exhibited but PML-RARA and t(15;17) were negative, variant APL needed to be considered, and fusion gene screen as well as RNA-sequencing should be displayed for making the diagnosis as soon as possible. Strikingly, we found that besides of RARA rearrangements, RARB or RARG rearrangements also generated the phenotype of APL. In addition, some MLL rearrangements, NPM1 rearrangements or others could also drove variant APL in absence of RARA/RARB/RARG rearrangements. These results indicated that one great heterogeneity existed in the genetics of variant APL. Among them, only NPM1-RARA, NUMA-RARA, FIP1L1-RARA, IRF2BP2-RARA, and TFG-RARA have been demonstrated to be sensitive to ATRA, so combined chemotherapy rather than differentiation induction therapy was the standard care for variant APL and these patients would benefit from the quick switch between them. If ATRA-sensitive RARA rearrangement was identified, ATRA could be added back for re-induction of differentiation. Through this review, we hoped to provide one integrated view on the genetic landscape of variant APL and helped to remove the barriers for managing this type of disease.

| S-EPMC8101136 | biostudies-literature

Notch signaling in acute promyelocytic leukemia.

Project description:Acute promyelocytic leukemia (APL) is initiated by the PML-RARA (PR) fusion oncogene and has a characteristic expression profile that includes high levels of the Notch ligand Jagged-1 (JAG1). In this study, we used a series of bioinformatic, in vitro, and in vivo assays to assess the role of Notch signaling in human APL samples, and in a PML-RARA knock-in mouse model of APL (Ctsg-PML-RARA). We identified a Notch expression signature in both human primary APL cells and in Kit+Lin-Sca1+ cells from pre-leukemic Ctsg-PML-RARA mice. Both genetic and pharmacologic inhibition of Notch signaling abrogated the enhanced self-renewal seen in hematopoietic stem/progenitor cells from pre-leukemic Ctsg-PML-RARA mice, but had no influence on cells from age-matched wild-type mice. In addition, six of nine murine APL tumors tested displayed diminished growth in vitro when Notch signaling was inhibited pharmacologically. Finally, we found that genetic inhibition of Notch signaling with a dominant-negative Mastermind-like protein reduced APL growth in vivo in a subset of tumors. These findings expand the role of Notch signaling in hematopoietic diseases, and further define the mechanistic events important for PML-RARA-mediated leukemogenesis.

| S-EPMC3872828 | biostudies-literature

The role of adjuvant chemotherapy in the management of acute promyelocytic leukemia differentiation syndrome.

Project description:Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone. We conducted a three-institution retrospective study, aiming to evaluate the role of short-term adjuvant chemotherapy in managing moderate DS for patients with low- or intermediate-risk APL initially treated with ATRA/ATO only protocols. We evaluated the difference in incidence and duration of moderate DS in APL patients who were treated with ATRA/ATO with or without adjuvant chemotherapy. 57 low- or intermediate-risk APL patients were retrospectively identified and included for this study; 36 patients received ATRA/ATO only induction treatment, and 21 patients received ATRA/ATO/adjuvant chemotherapy combination induction therapy. Similar proportions of patients experienced DS in both groups (66.7% vs. 81.0%, P = 0.246). The median duration of DS resolution in patients receiving ATRA/ATO only was 17 days (n = 23), and in patients receiving combination therapy was 8 days (n = 16) (P = 0.0001). The lengths of hospital stay in patients receiving ATRO/ATO only was 38 days (n = 7), and in patients receiving combination therapy was 14 days (n = 17) (P = 0.0007). In conclusion, adding adjuvant chemotherapy to ATRA/ATO only protocol may reduce the duration of DS and the length of hospital stay during APL induction treatment.

| S-EPMC9383033 | biostudies-literature

FISH-negative, cytogenetically cryptic acute promyelocytic leukemia.

Project description: Not available

| S-EPMC4648483 | biostudies-literature

Hypertriglyceridemia in Newly Diagnosed Acute Promyelocytic Leukemia.

Project description:The primary aim of the present retrospective study was to investigate lipid profiles and kinetics in acute promyelocytic leukemia (APL) patients. We analyzed 402 newly diagnosed APL patients and 201 non-APL patients with acute myeloid leukemia (as control). Incidence of hypertriglyceridemia in APL patients and non-APL patients was 55.82% and 28.4% (p = 0.0003). The initial levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were higher in APL patients than in control (all p < 0.0001). In APL patients, triglyceride levels were significantly increased during induction treatment with all-trans retinoic acid and arsenic. Multivariable analysis showed that age, being overweight (body mass index ≥25) and APL were independent risk factors for hypertriglyceridemia in all patients before treatment. High triglyceride levels were not significantly associated with disease-free survival or overall survival in the APL patients. In summary, in the current study triglyceride levels were significantly elevated in APL patients before treatment, and they increased during induction treatment, but there were no significant corresponding effects on survival.

| S-EPMC7724081 | biostudies-literature

Global characteristics of childhood acute promyelocytic leukemia.

Project description: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.

| S-EPMC4379131 | biostudies-literature

Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet.

Project description:Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion-based recommendations on the management of this disease. Together with providing current indications on genetic diagnosis, modern risk-adapted frontline therapy, and salvage treatment, the review contains specific recommendations for the identification and management of the most important complications such as the bleeding disorder APL differentiation syndrome, QT prolongation, and other all-trans retinoic acid- and ATO-related toxicities, as well as recommendations for molecular assessment of the response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. The most important challenges remaining in APL include early death, which still occurs before and during induction therapy, and optimizing treatment in patients with high-risk disease.

| S-EPMC6509567 | biostudies-literature

Oncogenic role of RARG rearrangements in acute myeloid leukemia resembling acute promyelocytic leukemia.

Project description:Acute myeloid leukemia (AML) featuring retinoic acid receptor-gamma (RARG) rearrangements exhibits morphological features resembling those of acute promyelocytic leukemia but is associated with drug resistance and poor clinical outcomes. However, the mechanisms underlying the role of RARG fusions in leukemogenesis remain elusive. Here, we show that RARG fusions disrupt myeloid differentiation and promote proliferation and self-renewal of hematopoietic stem and progenitor cells (HSPCs) by upregulating BCL2 and ATF3. RARG fusions overexpression leads to preleukemic phenotypes but fails to induce oncogenic transformation. However, the co-occurrence of RARG fusions and heterozygous Wt1 loss induce fully penetrant AML by activating MYC and HOXA9/MEIS1 targets. Leveraging Connectivity Map resources and high-throughput screening, we identify venetoclax, homoharringtonine, and daunorubicin as potential therapeutic options for RARG-AML. Overall, our findings provide pivotal insights into the molecular mechanisms governed by RARG fusions and enhanced by WT1 loss in AML development and propose a rational therapeutic strategy for RARG-AML.

| S-EPMC11729897 | biostudies-literature

Cytogenetically Cryptic Acute Promyelocytic Leukemia: A Diagnostic Challenge.

Project description:Cytogenetically cryptic acute promyelocytic leukemia (APL) is rare, characterized by typical clinical and morphological features, but lacks t(15;17)(q24;q21)/PML::RARA translocation seen in conventional karyotyping or FISH. The prompt diagnosis and treatment of APL are critical due to life-threatening complications associated with this disease. However, cryptic APL cases remain a diagnostic challenge that could mislead the appropriate treatment. We describe four cryptic APL cases and review reported cases in the literature. Reverse transcriptase polymerase chain reaction (RT-PCR) is the most efficient diagnostic modality to detect these cases, and alternative methods are also discussed. This study highlights the importance of using parallel testing methods to diagnose cryptic APL cases accurately and effectively.

| S-EPMC10488174 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data