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. 2020 Sep 25;9(10):3090.
doi: 10.3390/jcm9103090.

Absence of BCL-2 Expression Identifies a Subgroup of AML with Distinct Phenotypic, Molecular, and Clinical Characteristics

Inke De Haes  1 , Amélie Dendooven  2   3 , Marie Le Mercier  4 , Pauline Puylaert  5 , Katrien Vermeulen  4 , Mark Kockx  6 , Kathleen Deiteren  4 , Marie-Berthe Maes  4 , Zwi Berneman  1   7 , Sébastien Anguille  1   7
Affiliations

Absence of BCL-2 Expression Identifies a Subgroup of AML with Distinct Phenotypic, Molecular, and Clinical Characteristics

Inke De Haes et al. J Clin Med. .

Abstract

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the rapid and uncontrolled clonal growth of myeloid lineage cells in the bone marrow. The advent of oral, selective inhibitors of the B-cell leukemia/lymphoma-2 (BCL-2) apoptosis pathway, such as venetoclax, will likely induce a paradigm shift in the treatment of AML. However, the high cost of this treatment and the risk of additive toxicity when used in combination with standard chemotherapy represent limitations to its use and underscore the need to identify which patients are most-and least-likely to benefit from incorporation of venetoclax into the treatment regimen. Bone marrow specimens from 93 newly diagnosed AML patients were collected in this study and evaluated for BCL-2 protein expression by immunohistochemistry. Using this low-cost, easily, and readily applicable analysis method, we found that 1 in 5 AML patients can be considered as BCL-2-. In addition to a lower bone marrow blast percentage, this group exhibited a favorable molecular profile characterized by lower WT1 expression and underrepresentation of FLT3 mutations. As compared to their BCL-2+ counterparts, the absence of BCL-2 expression was associated with a favorable response to standard chemotherapy and overall survival, thus potentially precluding the necessity for venetoclax add-on.

Keywords: BCL-2; FLT3; acute myeloid leukemia; immunohistochemistry; next-generation sequencing; venetoclax.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
(A) Light micrographs of BCL-2 (B-cell leukemia/lymphoma-2, left) and corresponding haematoxylin and eosin (HE; middle) and CD34 stained paraffin sections of trephine biopsies from one representative acute myeloid leukemia patient with a BCL-2 H-score of 300; (B) bone marrow BCL-2 immunostains from two representative patients with H-scores of 300 (left panel), 150 (middle panel), and ≤20 (right panel). Thick black line = 50 µm.
Figure 2
Figure 2
Bone marrow WT1 transcript levels in the BCL-2− and BCL-2+ AML subgroups, with the black horizontal lines indicating the mean ± SEM values (copies/µg).
Figure 3
Figure 3
Kaplan–Meier overall survival curves of favorable/intermediate (A) and adverse (B) risk BCL-2− and BCL-2+ AML patients.
See this image and copyright information in PMC

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