Chr t(15;17)

P1, N=66, Active, not recruiting, National Cancer Institute (NCI)

P1/2, N=336, Completed, Forma Therapeutics, Inc. | Active, not recruiting --> Completed

P1/2, N=345, Completed, Celgene | Active, not recruiting --> Completed

However, the results of the present study confirmed that they may also be present in APL. Thus, these findings suggested a possible signaling pathway that involves the PML/RARA oncoprotein in APL.

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia that is distinguished by the chromosomal translocation t(15;17)(q24;q21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA). Recently, we identified a novel fusion gene in APL, RARA::ankyrin repeat domain 34C (ANKRD34C), identified its functions by morphological, cytogenetic, molecular biological and multiplex fluorescence in situ hybridization analyses, and demonstrated the potential therapeutic effect clinically and experimentally of all-trans retinoic acid (ATRA); the findings have important implications for the diagnosis and treatment of atypical APL.

P2, N=82, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=336, Active, not recruiting, Forma Therapeutics, Inc.

In Iranian APL patients, bcr1 predominates, while bcr3 correlates with higher WBC counts, high-risk categorization, additional chromosomal abnormalities, and faster CHR. Survival is negatively impacted by old age, relapse, lower PLT counts, higher WBC counts, and leukocytosis.

P1, N=30, Recruiting, Fred Hutchinson Cancer Center | Not yet recruiting --> Recruiting

P=N/A, N=20, Recruiting, The First Affiliated Hospital of Sun Yat-sen University; The First Affiliated Hospital of Sun Yat-sen University

P1, N=30, Not yet recruiting, Fred Hutchinson Cancer Center | Initiation date: Nov 2023 --> Feb 2024

Finally, we demonstrate how these models generate interpretable insights into which individual flow cytometric events and markers deliver optimal diagnostic utility, providing hematopathologists with a data visualization tool for improved data interpretation, as well as novel biological associations between flow cytometric marker expression and cytogenetic/molecular variants in AML. Our study is the first to illustrate the feasibility of using deep learning-based analysis of flow cytometric data for automated AML diagnosis and molecular characterization.

P1, N=16, Suspended, Syros Pharmaceuticals | N=24 --> 16 | Recruiting --> Suspended | Trial primary completion date: Apr 2024 --> Jan 2024

P1, N=153, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: Jul 2023 --> Jul 2024

RT-PCR for PML-RARA was positive for the bcr-3 transcript and FISH was positive for t(15;17) (q24;q21). The take home point from our case is to look for the presence of cells with bundle of Auer rods whenever there is pancytopenia with the presence of myelocyte-like cells with prominent granulations.

Composite karyotype, rare t(3;3) double minutes, +11,+13, del(9q), and del(Xq) were the novel findings reported in the South Canara region of Karnataka. Despite other molecular techniques, conventional cytogenetics remains the baseline in the diagnosis of malignancies.

Our findings confirm the lower age profile of AML in India and show similarities and differences with respect to the frequencies of individual abnormalities compared to the literature. The frequencies of the t(15;17), trisomy 8 and the high-risk abnormalities monosomy 7 and monosomy 5/del 5q were higher, and that of the inv(16), lower than in most reports.

P1, N=30, Not yet recruiting, Fred Hutchinson Cancer Center

Other abnormalities included t(1;19) and t(2;8)t(8;14). Cytogenetically favorable abnormalities are commonest occurring chromosomal defects in both Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan, i.e., t(8;21) in AML and Hyperdiploidy in ALL.

The cytogenetic data of adult AML from Pakistan showed presence of favourable prognostic karyotype with comparable prevalence as reported in international data. Moreover, FLT3/ITD mutations are commonly found in our patients as determined by molecular analysis. Therefore, inclusion of this unfavourable prognostic marker should be routine in molecular diagnostic testing of AML.

P1/2, N=336, Active, not recruiting, Novo Nordisk A/S | Trial completion date: Jul 2023 --> Feb 2024 | Trial primary completion date: Jun 2023 --> Dec 2023

In these two examples, the molecular abnormality allows us to better define the pathophysiology of leukemia, to adapt certain treatments (all-transretinoic acid, for example), and to follow up the residual disease of strong prognostic value beyond the simple threshold of less than 5% of marrow blasts, signaling the complete remission. However, the new sequencing techniques of the next generation open up broader perspectives by being able to analyze several dozens of molecular abnormalities, improving all levels of management, from diagnosis to prognosis and treatment, even if it means that morphological aspects are increasingly relegated to the background.

P1/2, N=84, Completed, University of Washington | Active, not recruiting --> Completed | Trial completion date: Feb 2027 --> Apr 2023

P2, N=76, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

In conclusion, this is the first comprehensive cytogenetic profile of Vietnamese patients diagnosed with de novo AML, which helps clinical doctors in prognostic classification for AML patients in Southern Vietnam.

Current first-line treatment of APL includes all-trans retinoic acid (all-trans RA), with or without arsenic trioxide, combined with chemotherapy, and a chemotherapy-free approach wherein arsenic trioxide is used alone or in combination with all-trans RA...The most recently published works on this subject highlight the development and optimization of carrier-based delivery systems based in microparticle formulations obtained by spray-drying to be used in the treatment of APL. The ultimate goal is to obtain a controlled delivery system for RA oral administration capable of providing a slow release of this bioactive compound in the intestinal lumen.

The use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) is highly effective making this now the most curable subtype of AML...On COG AAML1331, pediatric patients with HR APL were enrolled on a treatment arm that included the anthracycline idarubicin only in induction using a ATO-ATRA based regimen without maintenance therapy...Standard risk APL using a cytotoxic free ATO-ATRA induction also frequently results in hyperleukocytosis (elevated white blood cell count from blast differentiation) requiring cytoreduction. Thus, careful monitoring of these potential complications and aggressive supportive care to correct coagulopathy and treat differentiation syndrome and/or hyperleukocytosis is critical to prevent early death and ensure excellent cure rates.

P1, N=24, Recruiting, Syros Pharmaceuticals | Trial completion date: Mar 2023 --> Apr 2024 | Trial primary completion date: Mar 2023 --> Apr 2024

P1/2, N=345, Active, not recruiting, Celgene | Trial completion date: Dec 2022 --> Dec 2023

These cases exhibited TBL1XR1::RARB and KMT2A::SEPT6 fusions as well as mutations, e.g., NPM1 insertion and non-recurrent chromosomal aberrations. Our findings demonstrate the genetic diversity of AML with APL-like morphological features, which is of high importance for successful therapy implementation.

Most errors identified in the study were related to the interpretation of results. It was noted that the ELN guidance lacks clarity for certain clinical scenarios and highlights the requirement for urgent revision of the guidelines to elucidate these issues, and related educational efforts around the revisions to ensure effective dissemination.

P2, N=165, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

After ATRA and ATO dual induction and chemotherapy consolidation, the patient achieved complete remission (CR) with undetectable PML/RARα. However, the JAK2 V617F remained positive, and the patient developed MPN (PV/ET) 22 months later, which responded well to interferon therapy.AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; ATRA, all-trans retinoic acid; ATO, arsenic trioxide; BM, bone marrow; CR, complete remission; ET, essential thrombocythemia; Hb, hemoglobin; JAK2, Janus-associated kinase 2; MPN, myeloproliferative neoplasms; PLT, platelets; PMF, primary myelofibrosis; PML/RARα; PV, polycythemia vera; WBC, white blood cells.

The typical signal pattern for a positive RARA break-apart probe is one red, one green, and one fusion. In this study, we report a rare APL case with a PRKAR1A-RARA fusion gene with a signal pattern distinct from that of t(15;17) and its other variants.

Patients with low-risk APL are successfully treated using a chemotherapy-free combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). In this review, we explore the work that has gone into the modern-day diagnosis and highly successful treatment of this once devastating leukemia.

P3, N=276, Completed, Gruppo Italiano Malattie EMatologiche dell'Adulto | Active, not recruiting --> Completed

Our case had a unique presentation as the diagnosis of AML was very late after renal transplant. Managing the case was challenging as there is no consensus for this category of patients with the dilemma associated with their disease and the additional COVID-19 burden. Further studies are needed to validate a chemotherapy protocol for these patients.

Early death remains the major reason for treatment failure. Retrospective studies have reported an early death rate of 7.2-21.1%. In our population, it represents 16%. APL has progressed from a fatal disease to one that is highly curable in the last decade.

Early death remains the major reason for treatment failure. Retrospective studies have reported an early death rate of 7.2–21.1%. In our population, it represents 16%.

Thus, he received 5 days of mitoxantrone with etoposide, and BMA reassessment was in CR. The patient’s performance (PS) worsens after chemotherapy, so he continued subcutaneous cytarabine...He received dose-adjusted hydroxyurea with supportive measures, anticoagulant, and continued steroids... Our case had a unique presentation as the diagnosis of AML was very late after renal transplant. Managing the case was challenging as there is no consensus for this category of patients with the dilemma associated with their disease and the additional COVID-19 burden. Further studies are needed to validate a chemotherapy protocol for these patients.