Routine Diagnostic Immunophenotypic Profiling in AML Identifies Chemo Resistant Patients and Predicts Treatment Outcomes

Aim: This study aimed to examine different phenotypic stages of arrest observed in Acute Myeloid Leukemia.

Materials and Methods: A total of 220 patients with Acute Myeloid Leukemia (AML) were categorized into five subgroups Hematopoietic stem cells (HSCs), Multipotent Progenitors (MPPs), Common Myeloid Progenitors (CMPs), Common Myeloid Progenitors (CMPs), Granulocyte/Macrophage Progenitors (GMPs) based on their pattern of stage of leukemia arrest (SLA) using an Immunophenotypic profile with routine myeloid markers (MPO, CD13, CD33, CD14, HLADR, and CD34) at diagnosis and were correlated with clinicohematological parameters, molecular and cytogenetic characteristics, and disease status.

Results: The distribution of the SLA phenotypes showed 21% with MPP, 26% with CMP, 21% with GMP, and 37% with GP/MP and none of the patient showed HCP phenotype. In relation to clinicohematological parameters, male patients had maturation arrest at an earlier stage of differentiation (MPP/CMP), whereas female showed in a later stage (GP/MP). High white blood cell (WBC) and blast counts exhibited maturation arrest at the later stage (GP/MP. In relation with FAB subtypes, 83% AML-M3, 42% of AML-M4, and 50% of AML-M5 are associated with the GP/MP phenotype, while 67% of AML-M0 and 23% of AML-M1 are associated with the MPP phenotype. Further, maturation arrest at the MPP level was associated with aberrant CD7 expression. In relation with mutations in FLT3-ITD/ FLT3 D835 were associated with MPP (27%) and CMP (40%), C-kit mutations with CMP stage (67%), whereas NPM1 mutations (75%) and CEBPA mutations (50%) were showed arrest at the progenitor stage (GP/MP). In relation to treatment response, 75% with the MPP phenotype, 13% with CMP, 27% with GMP, and 19% with GP/MP showed persistent leukemic activity. This suggests that the MPP group is the most resistant to chemotherapy.

Conclusion: Acute Myeloid Leukemia Immunophenotyping can identify a new SLA phenotype that effectively correlates with leukemic cell behavior and helps predict major genetic subgroups at diagnosis, along with their response to standard intensive chemotherapy.