Acute myeloid leukemia with e1a2 BCR-ABL1 fusion gene: two cases with peculiar molecular and clinical presentations

Silva, Fernanda Borges da; Machado-Neto, João Agostinho; Koury, Luisa Corrêa de Araujo; Bertini, Virginia Helena Leira Lipoli; Ratis, Cristina Alonso; Chauffaille, Maria de Lourdes Lopes Ferrari; Velloso, Elvira Deolinda Rodrigues Pereira; Simões, Belinda Pinto; Rego, Eduardo Magalhães; Traina, Fabı́ola

doi:10.1016/j.bjhh.2017.07.001

Cited by 2 publications

(1 citation statement)

References 16 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies demonstrate that MECOM rearranged AML regardless of therapy has a poor prognosis with significantly lower overall survival, event‐free survival, and higher cumulative incidence of relapse. 14 , 15 , 16 BCR‐ABL1 rearranged cases are also reported to be associated with poor prognosis, and there is a need for aggressive treatment 17 for achieving optimal outcome. This will also hold true when both BCR::ABL1 and RUNX1::MECOM coexist.…”

Section: Discussionmentioning

confidence: 99%

A rare presentation of BCR‐ABL1 and RUNX1‐MECOM rearrangement in a pediatric patient with acute myeloid leukemia

Alamri,

Alanazi,

AlRajeh

et al. 2024

Clinical Case Reports

View full text Add to dashboard Cite

Key Clinical MessageIn 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.AbstractAcquisition 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.

show abstract