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t(3;21)(q26;q22) in myeloid leukemia
An aggressive syndrome of blast transformation associated with hydroxyurea or antimetabolite therapy
Article first published online: 10 MAR 2006
Copyright © 2006 American Cancer Society
Volume 106, Issue 8, pages 1730–1738, 15 April 2006
How to Cite
Cameron Yin, C., Cortes, J., Barkoh, B., Hayes, K., Kantarjian, H. and Jones, D. (2006), t(3;21)(q26;q22) in myeloid leukemia. Cancer, 106: 1730–1738. doi: 10.1002/cncr.21797
- Issue published online: 4 APR 2006
- Article first published online: 10 MAR 2006
- Manuscript Accepted: 4 NOV 2005
- Manuscript Revised: 10 OCT 2005
- Manuscript Received: 19 JUL 2005
- Kimberly Patterson Fellowship in Leukemia Research
- National Cancer Institute (NCI). Grant Number: CA16672
- chronic myeloid leukemia;
- therapy-related leukemia;
The t(3;21)(q26;q22) translocation is associated with myeloid leukemias and results in a chimeric oncoprotein containing AML1/RUNX1 variably fused to EAP, MDS1, and/or EVI1.
The current study describes what to the authors' knowledge is the first large case series reported to date of 26 t(3;21)(q26;q22)-associated leukemias, in which 24 cases arose after chemotherapy. Conventional G-band karyotyping and flow cytometry immunophenotyping were performed. Reverse transcriptase–polymerase chain reaction (RT–PCR) was performed to detect fusion transcripts between AML1 and EAP, MDS1, or EVI1, followed by DNA sequencing.
In all 16 patients with chronic myeloproliferative disorders, including 14 with chronic myelogenous leukemia (CML), the occurrence of t(3;21) heralded myeloid blast transformation. Fifteen (93%) patients had been previously treated with hydroxyurea. Eight patients with chronic myeloproliferative disorders (CMPD) were found to have t(3;21) with t(9;22) as the sole cytogenetic abnormality; in 5 other patients this was accompanied by trisomy 8. Among 10 cases of t(3;21)-associated acute myeloid leukemia, 8 were secondary tumors after chemotherapy for other neoplasms that had been treated with regimens including fludarabine and 5–fluorouracil in 3 patients each and etoposide in 2 patients. The immunophenotype of the blasts in all 22 tested cases was similar, with uniform expression of myeloid markers and CD34 and variable expression of CD7 and CD9, but minimal morphological myeloid maturation. Dysplastic micromegakaryocytes and bone marrow fibrosis were observed predominantly in CMPD cases. RT–PCR followed by DNA sequencing showed that the AML1-/MDS1-/EVI1 (AME) fusion transcript was detected in all 5 cases assessed. Among the patients with CMPD, 8 died of disease (at a median of 6.5 mos) and 5 achieved disease remission with bone marrow transplantation. Among patients with acute myeloid leukemia/myelodysplastic syndrome, 7 died of disease (at a median of 2 mos) and 2 had persistent leukemia with short follow-up.
Activation of AME through t(3;21) defines a highly aggressive, therapy-related leukemic blast syndrome. Prior treatment with hydroxyurea or other antimetabolites is implicated as a contributory cause. Cancer 2006. © 2006 American Cancer Society.