Pediatric acute erythroid leukemias with monocytic antigen expression and novel chromosomal translocations

Abstract

Acute erythroid leukemia (AEL) is a rare subtype of pediatric acute myeloid leukemia (AML) and is associated with a poor prognosis. [1][2][3] AEL can be primary, therapy related or secondary to other myeloid neoplasms, and can be subclassified as pure erythroid or mixed erythroid/myeloid leukemia, with the former having a poorer prognosis. 1,4 The genetic basis of AEL remains poorly defined, but previous genomic studies of adult and pediatric AELs identified enrichment of NUP98rearrangement and a wide spectrum of somatic mutations including high frequency of TP53 mutations. [4][5][6][7] Children Oncology Group (COG) reported recurrent NUP98-rearrangements in approximately 32% and the presence of complex karyotypes (≥3 abnormalities) in 29% of AEL patients (n = 24), but the majority lacked recurrent genetic abnormalities. 1 Although novel genetic abnormalities have been rarely reported in single case reports, 8,9 further studies on genetic abnormalities and immunophenotypes are warranted. Here, we report two AEL cases with novel chromosomal translocations.Patient 1 was a 2-month-old male, with sickle cell trait, who presented with a right shoulder mass. Biopsy showed diffuse infiltrate of atypical tumor cells, positive for CD43, CD71, GLUT1, and E-Cadherin by immunostain. The bone marrow aspirate (BMA) showed 81% blasts, morphologically compatible with erythroblasts. Flow cytometry confirmed the diagnosis of AEL with variable monocytic antigen expression of CD14. A fusion gene of CIC::NUT2MA was detected by next-generation sequencing (NGS). He received induction chemotherapy as per the standard arm of COG AAML1831 protocol and was minimal residual disease (MRD) negative on BMA at end of induction (EOI). Radiographic imaging showed marked response in the extramedullary disease burden at the EOI. Unfortunately, he died of disease progression 3 months following diagnosis. Patient 2 was a 2-year-old female, with bilateral hypoplastic thumbs but negative Fanconi Anemia work-up, who presented with pancytopenia. BMA identified 76% blasts, with a morphology compatible with erythroblasts. Flow cytometry identified abnormal blasts with erythroid (CD71, CD235a) and myeloid and monocytic differentiation (CD117, HLADR, CD64, CD14). The cytogenetic karyotyping showed 48,XX,t(1;8)(p34;q22),del(3)(p13p21),+6,+19 [13]/46,XX [7].