MYC protein expression is an important prognostic factor in acute myeloid leukemia

Abstract

As new drugs targeting MYC show clinical activity in acute myeloid leukemia (AML), understanding MYC expression in AML is of critical importance. We assessed MYC protein expression by immunohistochemistry in bone marrow of patients with untreated AML (n = 265). Overall, 90% of patients demonstrated MYC overexpression and MYC immunopositivity ≤6% was associated with superior complete remission (CR) duration of 23 months versus 12 months for MYC immunopositivity >6% (p = .028). Among 241 patients at higher risk for relapse, including those ≥55 years of age and patients with intermediate- and high-risk AML, MYC immunopositivity ≤6% conferred significantly superior median overall survival (OS) (24 versus 13 months; p = .042), event-free survival (EFS) (14 versus 6 months; p = .048), and relapse-free survival (RFS) (25 versus 12 months; p = .024). The prognostic impact of MYC-immunopositivity was retained on multivariate analysis of OS, EFS, and RFS. We conclude that MYC immunopositivity is an important prognostic factor in patients with untreated AML, particularly those at higher risk for relapse.

Prognostic significance of MYC oncoprotein expression on survival outcome in patients with acute myeloid leukemia with myelodysplasia related changes (AML-MRC)

“…Two previous studies have assessed the prognostic significance of MYC oncoprotein in AML patients 20,21 . In the first study performed by Mughal et al that included a total of 199 AML patients, high MYC level (IHC staining at or above median score and more than 1+ staining intensity) was associated with poor OS in patients with favorable and intermediate cytogenetic groups although it did not reach the statistical significance in the multivariate analysis adjusted by age and cytogenetic risk group 21 .…”

“…790-4628; prediluted) using Ventana Discovery XT automated system. We used 5% as cut-off (calculated as MYC positive cells out of total counted blasts in the selected area with sheets of blasts) as previously reported 20 .…”

“…Although the underlying oncogenic mechanism of MYC is unclear, a recent study showed that high levels of MYC expression is associated with inferior survival outcomes in de novo AML patients 20,21 . Compared to other subtypes of AML, AML-MRC patients were shown to have dynamic range of MYC protein expression 20 , yet the clinical significance of MYC expression in these unique patient population is unknown. Our study attempts to explore the prognostic impact of MYC protein levels on the survival outcomes in AML-MRC patients and assess somatic mutational landscapes in low vs. high MYC AML-MRC patients.…”

The Role of MYC and PP2A in the Initiation and Progression of Myeloid Leukemias

“…Different murine models, either using engraftment of hematopoietic precursors over-expressing MYC or transgenic mice, demonstrated the myeloid leukemogenic activity of MYC [37] and highlighted the significance of MYC-driven abrogation of apoptosis as key molecular mechanism [41,42]. In APL, MYC cooperates with PML-RARα to accelerate the development of leukemia [43], while in AML, MYC protein expression is a poor prognostic factor, particularly in patients with high risk of relapse [44,45]. It has been reported that the inhibition of MYC in AML cell lines drastically induces cell differentiation [46], and studies in mice have demonstrated that even transient inactivation of MYC yields tumor regression [47], supporting the hypothesis that targeting MYC regulation could be a highly pursued goal to treat cancer patients.…”

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa

“…MYC encodes a transcription factor and located in the chromosome 8q24. MYC is a proto-oncogene and involved in Burkitt lymphoma and multiple myeloma and serves as a prognostic factor in acute myeloid leukemia [ 106 ]. A study showed that asthmatics have increased MYC expression in peripheral blood ILC [ 107 ].…”