1Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.
2Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.
3Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.
A 29-year-old man was admitted to the hospital in April 2013 due to a newly developed fever. His hemogram results were: WBC count, 193,460/µL; Hb, 8.5 g/dL; and PLT, 21,000/µL. His peripheral blood smear (PBS) showed many leukemic blasts (93%) and bone marrow (BM) aspiration exhibited proliferation of leukemic blasts (91.8%) that tested positive for myeloperoxidase (MPO) using cytochemical staining. The blasts also tested positive for CD34, CD13, CD33, CD117, HLA-DR, MPO, and CD7 using immunophenotyping. The HemaVision (DNA technology, Aarhus, Denmark) result was negative for all detectable fusion transcripts and conventional karyotype analysis showed 46,XY . The FMS-like tyrosine kinase 3 internal tandem duplication (
In April 2015, the patient was re-admitted to hospital due to general weakness, and his PBS showed leukocytosis, thrombocytopenia (WBC count 12,550/µL; Hb, 15.5 g/dL; and PLT, 40,000/µL), and infiltration of leukemic blasts (60%). BM aspiration showed proliferation of leukemic blasts (80.0%) (Fig. 1A); the blasts showed identical immuophenotyping results (positive for CD34, CD13, CD33, CD1117, HLA-DR, MPO, and CD7) to those obtained at initial diagnosis and they also tested positive for MPO using a cytochemical stain (Fig. 1B). The patient's BM biopsy showed normocellular marrow (cellularity of 40%) and diffuse infiltration of leukemic blasts (Fig. 1C). His HemaVision result was also negative and the
However, we could not identify the translocated genes using metaphase FISH or RNA sequencing due to insufficient specimen quantity. Thus, we could not evaluate the genetic mechanism involving t(6;7) in AML, which is the main limitation of our report. Further studies focused on the identification of pathobiological mechanisms involving the t(6;7) clone in AML are required. In addition, since there was no report that showed t(6;7) in AML as a solitary major clone, we cannot evaluate whether the presence of t(6;7) in AML would be incidental or pathologic from the comparative analysis, and this would be an additional issue to be addressed.
When a new translocation of small clone size is developed at AML relapse after allogeneic HSCT, the possibility that this clone originated from the normal donor (so called constitutional translocation) should also be considered. However, a follow-up BM study of our patient after HSCT (in complete donor chimerism state) showed a normal karyotype, and this may be evidence that the minor t(6;7) clone detected in our case is not from the donor, but from the patient. Confirmation would require karyotype analysis using the fresh donor sample; however, we currently cannot perform this analysis, which is as an additional limitation of our study.
In conclusion, we report here a case with a solitary t(6;7)(p21.3;p22) passenger translocation that developed at relapse in an AML patient with a normal karyotype at the initial diagnosis. Genetic association between genes located in 6p21.3 and 7p22 in the pathogenesis of AML needs to be clarified in a future study.
Bone marrow aspiration (