1. Development of t(8;21) and RUNX1-RUNX1T1 in the Philadelphia-positive clone of a patient with chronic myelogenous leukemia: additional evidence for multiple steps involved in disease progression
- Author
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Ronald Hoffman, Leonard Issa, John Mascarenhas, Vesna Najfeld, Joseph Tripodi, Manpreet Sidhu, and Nathaniel Wisch
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Oncogene Proteins, Fusion ,Chromosomes, Human, Pair 21 ,Clone (cell biology) ,Trisomy ,Hematocrit ,Biology ,Trisomy 8 ,Translocation, Genetic ,Pathogenesis ,Chromosome 15 ,Young Adult ,RUNX1 Translocation Partner 1 Protein ,hemic and lymphatic diseases ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Proto-Oncogene Proteins ,Genetics ,medicine ,Humans ,Philadelphia Chromosome ,Molecular Biology ,In Situ Hybridization, Fluorescence ,Aged ,medicine.diagnostic_test ,Cytogenetics ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Immunology ,Core Binding Factor Alpha 2 Subunit ,Disease Progression ,Female ,Bone marrow ,Blast Crisis ,Chronic myelogenous leukemia ,Chromosomes, Human, Pair 8 ,Transcription Factors - Abstract
A 65-year-old patient with a high hemoglobin and hematocrit was treated for 14 months with therapeutic phlebotomy when cytogenetics of bone marrow revealed 100% cells with the Ph chromosome and 45% of the Ph+ cells contained trisomy 8. Treatment with tyrosine kinase inhibitors did not reduce the BCR-ABL1 fusion positive clone. Instead, the Ph positive cells acquired further the t(8;21)/ RUNX1-RUNX1T1 , del(4q) and trisomy 15 chromosomal abnormalities which were resistant to further treatment. Literature review revealed eight other patients who either had t(9;22) and t(8;21) simultaneously or developed t(8;21) in the Ph positive clone. We conclude that there are rare patients with CML who either present in blast crisis with coexistence of t(9;22) and t(8;21) with or without +8, or progress to blast crisis with acquiring RUNX1-RUNX1T1 in the BCR-ABL1 clone which may or may not be therapy related and represent a later event in a multistep pathogenesis.
- Published
- 2010