Acute myeloid leukemia with RAM immunophenotype: A report of three patients and comprehensive literature review

Introduction

The RAM immunophenotype (IP) in acute myeloid leukemia (AML) is defined by blasts with bright CD56 and weak-to-negative CD45, HLA-DR, and CD38 expression. A RAM IP predominantly presents in infants who have “standard-risk disease” under current criteria but, when treated accordingly, have devastatingly high rates of minimal residual disease and relapse with lower 3-year and overall survival rates. However, given the relative rarity of this phenotype, it is neither well-defined nor readily diagnosed.

Methods

We reviewed the electronic medical records of our institution from 1990 to 2024 for cases of AML expressing bright CD56 on flow cytometry and identified three cases with a RAM IP. Further, we performed a thorough literature search and reviewed impactful studies on pediatric AML and case/series reports of patients with a RAM IP, leading to the identification of 38 more cases.

Results

A total of 41 patients were collected. These patients were toddler age (1–3 years) with an equal sex distribution and clinically presented with low circulating blasts and cytopenias. Blasts were typically French–American–British M0 or M7. Immunophenotypically, CD33 and CD117 showed positivity in >90% of cases, with CD19, CD34, CD41, and CD42b, frequently positive. Half of the cases were positive for CD7 and CD61. T-cell/myeloid markers were rare, except for cytoplasmic CD3, seen in 1/3, apparently correlating with CBFAT2T3:GLIS1 fusions. Gains in chromosomes 21, 13, and 8 and CBFAT2T3::GLIS1 fusions were frequent.

Conclusion

AML with a RAM IP has a poor prognosis. This study offers a detailed characterization of the clinicopathologic patterns associated with this rare entity, which may help formulate the most appropriate diagnostic approach.