Chr t(15;17)/PML-RARA fusion

Diagnosis relies on clinical, morphological, phenotypic, and cytogenetic evidence, with treatment involving all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Hypogranular acute promyelocytic leukemia (AML3v) is a rare form and is even rarer when it is discovered following an ischaemic event, which is what makes our case so special.

This is the first report of an insertional PML::RARA fusion into the RARA gene on 17q detected by OGM. OGM has demonstrated its utility in a clinical cytogenetics environment, allowing for clearer characterization and diagnosis of various neoplasms.

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.

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

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

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.