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Assessment of the Metabolic Profile of Primary Leukemia Cells
Published on: November 21, 2018
Genetic Characterization of Pediatric Mixed Phenotype Acute Leukemia (MPAL)
Ioannis Panagopoulos1, Kristin Andersen2, Inga Maria Rinvoll Johannsdottir3
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; ioannis.panagopoulos@rr-research.no.
Background/Aim:
Mixed phenotype acute leukemia (MPAL) is a rare hematologic malignancy in which the leukemic cells cannot be assigned to any specific lineage. The lack of well-defined, pathogenetically relevant diagnostic criteria makes the clinical handling of MPAL patients challenging. We herein report the genetic findings in bone marrow cells from two pediatric MPAL patients.
Patients And Methods:
Bone marrow cells were examined using G-banding, array comparative genomic hybridization, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization.
Results:
In the first patient, the genetic analyses revealed structural aberrations of chromosomal bands 8p11, 10p11, 11q21, and 17p11, the chimeras MLLT10::PICALM and PICALM::MLLT10, and imbalances (gains/losses) on chromosomes 2, 4, 8, 13, and 21. A submicroscopic deletion in 21q was also found including the RUNX1 locus. In the second patient, there were structural aberrations of chromosome bands 1p32, 8p11, 12p13, 20p13, and 20q11, the chimeras ETV6::LEXM and NCOA6::ETV6, and imbalances on chromosomes 2, 8, 11, 12, 16, 19, X, and Y.
Conclusion:
The leukemic cells from both MPAL patients carried chromosome aberrations resulting in fusion genes as well as genomic imbalances resulting in gain and losses of many gene loci. The detected fusion genes probably represent the main leukemogenic events, although the gains and losses are also likely to play a role in leukemogenesis.
Insights
Genetic analysis of two pediatric mixed phenotype acute leukemia (MPAL) patients revealed chromosomal aberrations and fusion genes. These genetic alterations, including gains and losses, likely drive leukemogenesis in MPAL.
Area of Science:
- Hematology
- Genetics
- Oncology
Background:
- Mixed phenotype acute leukemia (MPAL) is a rare hematologic malignancy with unclear lineage.
- Diagnostic challenges exist due to the lack of well-defined criteria for MPAL.
- Understanding the genetic underpinnings of MPAL is crucial for improved patient management.
Purpose of the Study:
- To investigate the genetic findings in bone marrow cells of two pediatric MPAL patients.
- To identify specific chromosomal aberrations and fusion genes associated with MPAL.
- To contribute to a better understanding of MPAL pathogenesis.
Main Methods:
- G-banding
- Array comparative genomic hybridization (aCGH)
- RNA sequencing
- Reverse transcription polymerase chain reaction (RT-PCR)
- Sanger sequencing
- Fluorescence in situ hybridization (FISH)
Main Results:
- Patient 1: Structural aberrations (8p11, 10p11, 11q21, 17p11), MLLT10::PICALM/PICALM::MLLT10 chimeras, and chromosomal imbalances (gains/losses on 2, 4, 8, 13, 21), including a RUNX1 locus deletion.
- Patient 2: Structural aberrations (1p32, 8p11, 12p13, 20p13, 20q11), ETV6::LEXM/NCOA6::ETV6 chimeras, and chromosomal imbalances (gains/losses on 2, 8, 11, 12, 16, 19, X, Y).
- Both patients exhibited fusion genes and genomic imbalances.
Conclusions:
- Leukemic cells in both MPAL patients harbored chromosome aberrations leading to fusion genes and genomic imbalances.
- Detected fusion genes are likely the primary leukemogenic events in MPAL.
- Genomic gains and losses may also contribute significantly to MPAL development.
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