ACUTE MYELOID LEUKEMIA WITH A RARE IMMUNOPHENOTYPE AND COMPLEX GENETIC PROFILE

Abstract

Acute Myeloid Leukemia (AML) presents a wide immunophenotypic variability and defining molecular alterations, used for the revised WHO 2022 classification. The genetic profile is also used for risk stratification according to the European LeukemiaNet (ENL) 2021 and treatment definition. Here we present a case with an unusual immunophenotype and complex genetic alterations. Case report: 42-year-old woman, with increased menstrual flow in the last 10 days and no other alterations. On physical examination, she was in good condition, with slight paleness, without hemorrhagic suffusions, absence of lymph node enlargement and hepatosplenomegaly. Complementary tests showed Hb 9.4 g/dL WBC 2850/mm3 (2% blast cells) Platelets 48,000/mm3 Fibrinogen 56 mg/dL (normal: 200 – 400), normal biochemistry and coagulogram. The myelogram showed massive infiltration by hyper granular blasts suggesting basophilic leukemia. Immunophenotyping revealed 3 blast populations, all expressing cyMPObright, CD13, CD33bright, CD34, CD38dim/negative, CD44, CD45intermediate, CD45RA, CD96, CD97, CD99, CD123, CD244, CLL1, TIM3. The differences between the expressions of the blast populations were: 1st population (41%) expressed partial CD7, CD117bright and homogeneous, heterogeneous HLA-DR (positive to negative), not expressing CD11b and CD203c; 2nd population (40%) expressed CD11b, CD203c bright, without expressions of CD7 and HLA-DR (basophilic component); 3rd population (19%) did not express CD7, CD11b, CD203c and HLA-DR (promyelocytic component). The 3 populations did not express cyCD3, SmCD3, CD4, CD10, CD14, CD15, CD16, CD19, CD36, CD42a+CD61, CD54, CD56, CD64, CD71, cyCD79a, CD105, CD300e. This profile was consistent with AML with basophilic and acute promyelocytic (APL) components. The karyotype was complex: 46,XX, del(3)(p21),del(5)(q15), t(15;17)(q22;q21)[6]/46,XX[14]. The NGS panel revealed the presence of the PML::RARA gene fusion, negative for NPM1, FLT3 ITD and TKD mutations and others. The patient was treated with Cytarabine plus Daunorubicin (7+3) and ATRA. Assessment of measurable residual disease (MRD) by flow cytometry (FC) on D28 of induction showed 0.2% non-APL myeloblasts and 0.29% basophilic blasts. Despite preventive therapies, the patient experienced life-threatening bleeding and sepsis, but had a favorable outcome. She received 2 cycles of consolidation and maintenance therapy. FC MRD and PML::RARA RT-PCR was undetectable after the 2 consolidation cycles and during maintenance therapy. PML::RARA was also undetectable at the end of therapy and 3 months later. The probability of severe bleeding in APL with the concomitant presence of basophilic blasts has already been described, as was seen in this case. The patient had a good therapeutic response. Monitoring MRD in AML is essential to guide treatment, and the methods must be complementary, especially in cases with multiple leukemic clones. The identification of different leukemia clones by immunophenotype reflected the genetic complexity of this case. Therefore, it is important to integrate diagnostic methods for better patient management.