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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Clonal evolution and devolution after chemotherapy in adult acute myelogenous leukemia
Brian Parkin1, Peter Ouillette, Yifeng Li
1Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Blood
|November 24, 2012
Summary
Relapsed acute myeloid leukemia (AML) arises from the same original clone, not new ones. Chemotherapy may fail to eliminate all cancer cells, leading to disease persistence or relapse.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Acute myeloid leukemia (AML) frequently relapses or persists after induction chemotherapy.
- Understanding the clonal evolution of AML is crucial for improving treatment outcomes.
Purpose of the Study:
- To investigate the clonal relationship of AML in relapsed and persistent disease phases.
- To determine the origins of relapsed and persistent AML after chemotherapy.
Main Methods:
- Genomic profiling using SNP 6.0 arrays to identify acquired copy number aberrations (aCNA) and copy neutral loss of heterozygosity (cnLOH).
- Sequence analysis of recurrently mutated genes in paired AML samples (presentation and relapse/persistence).
- Analysis of 39 paired AML samples from patients with relapsed (28 pairs) or persistent (11 pairs) disease.
Main Results:
- Relapsed AML consistently originates from the re-emergence or evolution of a founder clone present at diagnosis.
- All copy number aberrations (aCNA) and copy neutral LOH (cnLOH) detected at initial presentation were retained in relapsed samples, indicating their role in AML evolution.
- Persistent AML cases sometimes involved two coexisting dominant clones, with one being chemotherapy-sensitive and the other resistant.
Conclusions:
- AML relapse and persistence are primarily caused by the incomplete eradication of founder clones, not the emergence of entirely new clones.
- These findings have significant implications for developing targeted therapies and refining clinical AML research strategies.
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