Acute promyelocytic leukemia (APML) with variant RARa translocations comprises 1-2% of APML cases. However, the diagnosis of these cases is challenging as the routine practice includes fluorescence in situ hybridization (FISH) reverse transcription polymerase chain reaction targeting the PML and RARA genes to detect PML/RARA fusions. Here, we report a case highlighting the importance of atypical FISH signal patterns in standard dual-color dual-fusion PML/RARa FISH analysis complimented by karyotyping to detect these variant RARA translocations.

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http://dx.doi.org/10.1016/j.hemonc.2016.12.003DOI Listing

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Introduction: Acute promyelocytic leukemia (AML-M3), classified as acute Myeloid leukemia with PML RARA according to the 5th edition of the World Health Organization classification of haematolymphoid tumors 2022 [1], is marked by abnormal promyelocyte proliferation and is known for high risks of bleeding and thromboembolic complications. We present a case where lower limb ischemia revealed this leukemia in a child.

Case Report: An 11-year-old with minor ankle trauma developed severe lower limb ischemia, leading to the discovery of subtotal femoral artery thrombosis.

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  • - Variant acute promyelocytic leukemia (vAPL) is a specific type of APL that involves atypical fusion proteins, which are difficult to identify using standard methods like PCR and FISH, necessitating newer techniques like next-gen sequencing.
  • - Patients with vAPL often show resistance to traditional treatments like arsenic trioxide and all trans-retinoic acid, leading to ambiguous prognoses, but venetoclax (VEN) has demonstrated effectiveness when combined with ATRA.
  • - This research presents the first recorded case of vAPL with a TFG-RARA fusion gene successfully treated with VEN and ATRA, achieving complete remission, suggesting that VEN could improve outcomes for vAPL patients.
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  • Variant acute promyelocytic leukemia (APL) presents challenges in diagnosis and treatment due to the lack of certain indicators, complicating effective patient management.
  • A case report details a patient with ATRA-resistant APL characterized by a specific fusion gene who successfully entered complete remission after treatment with venetoclax, azacitidine, and ATRA.
  • The patient faced additional health issues, including pulmonary tuberculosis and a multidrug-resistant infection, which showed significant improvement following targeted treatments.
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Fusion genes generally serve as driver mutations in leukemia. The rearrangement of the RARA gene located on chromosome 17q21 is a molecular pathological feature of acute promyelocytic leukemia (APL). A series of RARA-involved fusion genes have been identified in variant APL, including one carrying the t(11;17)(q13;q21) translocation, resulting in the NUMA1::RARA fusion gene.

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The present study described an extremely rare case of acute promyelocytic leukemia (APL) characterized by a complex three‑way (15;22;17)(q22;q11.2;q21) translocation. Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia with distinctive clinical and therapeutic characteristics.

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