Ollier Disease, Acute Myeloid Leukemia, and Brain Glioma: IDH as the Common Denominator

TL;DR

This study finds that a specific IDH1 gene mutation is common to three different cancers in the same patient, suggesting a shared cause and potential targeted treatment.

Contribution

The study identifies the IDH1-R132H mutation as a shared genetic cause among Ollier disease, brain glioma, and acute myeloid leukemia in a single patient.

Findings

The IDH1-R132H mutation was found in all three diseases in one patient and in 100% of Ollier disease and brain glioma cases studied.

This mutation is proposed as a potential target for new therapies across these diverse cancers.

Only one patient with all three diseases was identified, highlighting the rarity and significance of the shared mutation.

Abstract

Thanks to the continuous refinement of diagnostic tools, the role of molecular markers analysis has become even more decisive in tumor diagnosis and classification and, accordingly, in the decision-making process of treatment, as emphasized by the most recent WHO Classification of the Tumors of the Central Nervous System (2021), and also by the WHO Classification of Hematolymphoid Tumors (2022). In this setting, the possibility to identify a genetic mutation common to three apparently completely different neoplasms, such as enchondromatosis, acute myeloid leukemia, and brain glioma, and affecting the same patient not only provides a better understanding of the bases of tumorigenesis but also opens the doors to the development of new targeted therapies and experimental treatments which could be effective for apparently different diseases. The present study identified in the IDH1-R132H gene mutation the etiopathogenetic common denominator among Ollier disease, brain glioma, and acute myeloid leukemia coexisting in the same patient.

Ollier disease (OD), acute myeloid leukemia (AML), and brain glioma (BG) are three apparently completely different neoplasms in terms of histopathology, clinic, natural history, and management, but they can affect the same patient. This study aimed to identify the common molecular pathways involved in the pathogenesis of all three diseases and discuss their current and potential role as therapeutic targets. A detailed and comprehensive systematic literature review according to PRISMA guidelines on OD patients harboring BG and/or AML was made. In addition, the unique case of a patient affected by all three considered diseases has been added to our case series. Demographic, pathological, treatment, and outcome data were analyzed and discussed, mainly focusing on the molecular findings. Twenty-eight studies reported thirty-three patients affected by OD and BG, and only one study reported one patient with OD and AML, while only our patient harbored all three pathologies. The IDH R132H mutation was the only genetic alteration shared by all three pathologies and was simultaneously detected in enchondromas and brain glioma in 100% (3/3) of OD patients with BG and also in the neoplastic blood cells of the single patient hosting all three diseases. The IDH1-R132H gene mutation is the etiopathogenetic common denominator among three apparently different tumors coexisting in the same patient. The adoption of mutant-specific IDH1 inhibitor molecules could represent a potential panacea for these conditions in the era of targeted therapies. Further studies with larger clinical series are needed to confirm our results and hypothesis.

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