Chromosome 1 Alterations in Multiple Myeloma: Considerations for Precision Therapy

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Multiple myeloma (MM) is an incurable plasma cell malignancy.
• High-risk MM, characterized by cytogenetic abnormalities, has poor prognosis and therapeutic challenges.
• Current targeted therapy for MM is limited, with venetoclax approved only for t(11;14).

Purpose of the Study:

• To review emerging precision therapies for multiple myeloma targeting chromosome 1 abnormalities.
• To explore novel therapeutic strategies for high-risk MM patients with specific genetic alterations.

Main Methods:

• Review of current literature on gene therapies, small molecule inhibitors, and monoclonal antibodies.
• Focus on agents targeting oncogenic drivers in chromosome 1 regions (e.g., MCL-1, BCL9, F11R, CKS1B).

Main Results:

• Chromosome 1q gains, amplifications, and 1p deletions are common in MM and associated with drug resistance and poor prognosis.
• Several novel therapies are under investigation to target key genes within these regions.
• These emerging therapies aim to antagonize drivers of cell survival, proliferation, and drug resistance.

Conclusions:

• Chromosome 1 abnormalities represent a significant driver of high-risk MM.
• Targeting genes within these abnormal regions offers a promising precision medicine approach.
• This strategy could benefit a patient population with limited effective treatment options.