X chromosome insertion in the MLL gene in a case of childhood acute myeloblastic leukemia

Area of Science:

• Genetics
• Oncology
• Hematology

Background:

• The 11q23 chromosomal band is frequently implicated in translocations and insertions, leading to Mixed Lineage Leukemia (MLL) gene rearrangements.
• MLL gene rearrangements are a known mechanism in various hematologic malignancies, including acute myeloblastic leukemia (AML).

Observation:

• A 5-month-old boy diagnosed with acute myeloblastic leukemia (AML) M4 subtype presented with hemianopsia and severe diffuse intravascular coagulopathy.
• Conventional cytogenetics revealed an insertion at chromosome 11q23 involving chromosome Xq28q12: ins(11;X)(q23;q28q12).
• Fluorescent in situ hybridization (FISH) confirmed the insertion and demonstrated MLL gene disruption, with a segment of the X chromosome inserted within the MLL gene.

Findings:

• This case represents the first reported instance of an insertion involving the MLL gene and band Xq28.
• The specific chromosomal rearrangement resulted in the MLL gene being fractured, with a portion of the X chromosome inserted between its 5' and 3' regions.
• It is postulated that this rearrangement led to the fusion of the MLL gene's 5' region with an unidentified gene located at Xq28.

Implications:

• This unique chromosomal abnormality provides novel insights into the diverse mechanisms of MLL gene involvement in pediatric AML.
• The identification of a novel gene fusion resulting from this insertion may have implications for understanding leukemogenesis and developing targeted therapies.
• Further investigation into the gene at Xq28 is warranted to fully elucidate its role in this specific AML case.