High-Risk Microgranular Acute Promyelocytic Leukemia with a Five-Way Complex Translocation Involving PML-RARA

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Acute promyelocytic leukemia (APL) is typically caused by the t(15;17) translocation, forming the PML-RARA fusion gene.
• The hypogranular variant of APL presents unique morphological characteristics.
• Genetic complexity in APL can influence disease presentation and treatment response.

Purpose of the Study:

• To report the first documented case of APL resulting from a 5-way chromosomal translocation.
• To describe the clinical presentation, diagnostic findings, and treatment of this unique APL case.
• To evaluate the efficacy of all-trans retinoic acid (ATRA) in APL with complex chromosomal abnormalities.

Main Methods:

• Case report of a 50-year-old male patient with acute leukemia symptoms.
• Morphological examination of leukemic blasts.
• Fluorescence in situ hybridization (FISH) and cytogenetic analysis to identify chromosomal translocations.
• Molecular testing for PML-RARA fusion transcripts.
• Treatment with ATRA, conventional chemotherapy, and intrathecal chemotherapy for CNS prophylaxis.

Main Results:

• The patient presented with symptoms consistent with APL, including a hypogranular blast morphology.
• FISH and cytogenetic analysis revealed a novel 5-way translocation: 9q34, 17q21, 15q24, 12q13, and 15q26.1.
• Molecular testing confirmed PML/RARA fusion transcripts.
• The patient achieved complete remission after treatment with ATRA and chemotherapy.
• The patient remains in remission on maintenance therapy.

Conclusions:

• This is the first reported case of APL associated with a 5-way chromosomal translocation.
• The patient's prompt response to ATRA-containing therapy suggests similar efficacy to other APL subtypes with PML-RARA fusion.
• Complex chromosomal translocations in APL, while rare, do not preclude successful treatment with standard APL regimens.