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Complex variant t(4;11) characterized by fluorescence in situ hybridization in infant acute lymphoblastic leukemia
1Department of Cytogenetics, New Children's Hospital, Hawkesbury Rd., Westmead, Australia.
Insights
A rare two-step translocation involving chromosomes 4 and 11 was identified in a child with acute lymphoblastic leukemia (ALL). This complex chromosomal abnormality impacts the MLL gene, offering insights into leukemia development.
Area of Science:
- Cytogenetics
- Molecular Biology
- Pediatric Oncology
Background:
- Acute lymphoblastic leukemia (ALL) is a common childhood cancer.
- Chromosomal translocations are frequently observed in ALL, often driving disease pathogenesis.
- The t(4;11)(q21;q23) translocation is a known recurrent abnormality in ALL, typically involving the MLL gene.
Observation:
- A 6-month-old female diagnosed with ALL presented with an atypical 11p appearance on the derivative chromosome 11.
- Standard cytogenetic analysis revealed a 46,XX,t(4;11)(q21;q23) karyotype.
- Fluorescence in situ hybridization (FISH) studies were performed using multiple probes, including whole chromosome paints, arm-specific paints, subtelomere probes, and an MLL gene probe.
Findings:
- FISH analysis elucidated a complex, two-step translocation event.
- The initial translocation was a standard t(4;11)(q21;q23).
- A subsequent translocation occurred between the two derivative chromosomes, leading to an altered MLL gene position and splitting.
Implications:
- This case highlights a rare, complex chromosomal rearrangement in pediatric ALL.
- The findings demonstrate how sequential translocations can create novel genetic alterations.
- Understanding these complex rearrangements is crucial for accurate diagnosis and potentially for developing targeted therapies in ALL.
Abstract:
A 6-month-old girl was diagnosed with acute lymphoblastic leukemia (ALL). Chromosome analysis of bone marrow aspirate showed 46,XX,t(4;11)(q21;q23) with an atypical appearance of the 11p on the der(11) chromosome. FISH studies to fully characterize the translocation utilised 8 probes: whole chromosome painting probes for chromosome 11 and chromosome 4; separate chromosome 11 short arm and long arm paints; specific subtelomere probes from 11p, 11q, and 4q; MLL gene probe. Taken together, the results indicated a two-step abnormality: an initial standard t(4;11)(q21;q23), followed by another t(4;11)--this time, between the two derivative chromosomes. The MLL gene was split by the first translocation and its position altered by the second.