# A New Histology-Based Prognostic Index for Acute Myeloid Leukemia: Preliminary Results for the “AML Urayasu Classification”

## TL;DR

This study introduces a new classification system for acute myeloid leukemia based on protein expression patterns to predict patient prognosis and treatment resistance.

## Contribution

The Urayasu classification is a novel histology-based prognostic index for AML that identifies treatment resistance mechanisms and improves patient stratification.

## Key findings

- Four key proteins (p53, MRP1, AKR1B10, AKR1B1) were linked to treatment resistance and prognosis in AML patients.
- Group 1 patients had the best 5-year survival rate (82–100%) based on specific protein expression profiles.
- Group 3 patients showed the poorest prognosis with a median survival of 12–14 months and 0% 2-year survival.

## Abstract

Background: This study was aimed at elucidating the mechanisms underlying the development of treatment resistance in patients with acute myeloid leukemia (AML) other than M3 myeloid leukemia in order to devise ways to overcome treatment resistance and improve the treatment outcomes in these patients. Methods: For this study, we randomly selected 35 patients with AML who had received combined cytarabine plus idarubicin treatment for new-onset AML at our hospital. We performed immunohistochemical analysis of biopsy specimens obtained from the patients to investigate the expressions of 23 treatment-resistance-related proteins, and retrospectively analyzed the correlations between the expression profiles of the resistance proteins and the patient survival. Results: The following four proteins were identified as being particularly significant in relation to treatment resistance and patient prognosis: (1) p53; (2) multidrug resistance-associated protein 1 (MRP1; idarubicin extracellular efflux pump); (3) aldo-keto reductase family 1 member B10 (AKR1B10; idarubicin-inactivating enzyme); and (4) AKR1B1 (competitive inhibitor of AKR1B10). Based on our findings, we propose the following Urayasu classification for AML, which we believe would be very useful for accurately stratifying patients with AML according to the predicted prognosis: Group 1 (n = 22, 63%): p53(-)/MRP1(-) associated with AKR1B10(+)/AKR1B1(+) or AKR1B10(-)/AKR1B1(-); 5-year overall survival (OS), 82%–100%; Group 2 (n = 9, 26%): p53(-)/MRP1(-) associated with AKR1B10(+)/AKR1B1(-); 5-year OS, 68%; Group 3 (n = 4, 11%): p53(+) or MRP1(+); median survival, 12–14 months; 2-year OS, 0%. Conclusions: The Urayasu classification for AML is useful for predicting the prognosis of patients with AML. Group 1 in this classification included twice as many patients as that included in the Favorable prognosis group in the AML prognostic classification proposed by the European Leukemia Net. As the Urayasu classification for AML is based on the mechanisms of resistance to chemotherapy, it is not only useful for prognostic stratification of the patients, but also provides insights for developing more effective treatments for AML.