ABSTRACT
Key Clinical Message: In a patient with de novo AML, co-existing BCR::ABL1 p190 isoform and RUNX1::MECOM rearrangement is accompanied by a very poor prognosis including limited response to treatment and no molecular remission. It is essential to develop a consensus on the therapeutic modalities different from the current regimen. Abstract: Acquisition of BCR::ABL1 fusion as a primary or secondary event and RUNX1::MECOM fusion independently is reported in de novo and therapy-related MDS/AML, albeit with low frequency (<0.5%). Coexistence of BCR::ABL1 and MECOM translocation is known to cause leukemogenesis in animal models and progression towards blast crisis CML but not AML. Here we report a unique case of pediatric AML with concomitant BCR::ABL1 and RUNX1::MECOM fusion.Routine diagnostic work-up included WBC manual differential, immunophenotype, morphology, qPCR, FISH, and NGS-based CNV analyses. The patient presented with history of fever, dizziness, fatigue, gingival bleeding, and epistaxis associated with ecchymosis in right hand and heavy, prolonged menstrual period. At presentation, her hemoglobin was 5.3 g/dL, WBC 52.1(10*9/L), PLT 10(10*9/L), ESR 5 mm/h and LDH 2658 U/L. Bone marrow was hypercellular with 71% blasts, and flow cytometry showed myeloid markers including CD11c, CD33, CD34, and CD45 among others indicating AML with monocytic differentiation. FISH analyses showed variant t(9;22) (q34.1;q11.1), one additional copy each of chromosome 8 and Runx1 gene, while NGS-based CNV analyses revealed a terminal and proximal pathogenic gain within 9q34.12q34.3 and 22q11.1q11.23, respectively, and gain of entire chromosome 8 and 12 in mosaic state. qPCR confirmed the presence of p190 and also revealed RUNX1::MECOM fusion. Patient received ADE (cytarabine, daunorubicin, and etoposide) induction regimen but required multiple ICU admissions due to sepsis, cardiac shock, acute myocarditis, and thyroiditis. Coexisting BCR::ABL1 and RUNX1::MECOM fusion is suggestive of poor prognosis, and a need for consensus on the treatment modalities other than the current regimen is warranted.
ABSTRACT
Key Clinical Message: Complete molecular remission in a "variant APL" patient with short isoform of PML-RARα and FLT3-ITD mutation was achieved in response to ATRA and ATO plus IDA instead of standard treatment protocol. The use of FLT3 inhibitor in APL induction management is implicated to prevent differentiation syndrome and coagulopathy experienced in in patients with FLT3-ITD. Abstract: FLT3-ITD mutations are the most common activating mutations in FLT3 gene, occurring in about 12 to 38% of acute promyelocytic leukemia cases, and are mainly associated with high white blood cell counts and poor clinical outcomes. Here, we present a case of APL variant with adverse prognostic features who showed short isoform [bcr3] of PML-RARα and FLT3-ITD mutation at diagnosis. The patient received all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) plus idarubicin (IDA) instead of standard treatment protocol, and achieved a complete morphological, cytogenetic and molecular response. However, the patient experienced differentiation syndrome, and coagulopathy that was subsequently resolved by continuous oxygen therapy, dexamethasone, and enoxaparin. The use of FLT3 inhibitor in APL induction management is implicated to prevent differentiation syndrome and coagulopathy in patients with FLT3-ITD mutation.
