Abstract:
:3q26.2/EVI1 rearrangements resulting in EVI1 overexpression play an important role in leukemogenesis and are associated with treatment resistance and a poorer prognosis in patients with acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia and BCR-ABL negative myeloproliferative neoplasms. In this study, we aim to explore the clinicopathological features of myelodysplastic/myeloproliferative (MDS/MPN) neoplasms with 3q26.2/EVI1 rearrangements and determine the potential impact of these cytogenetic abnormalities on treatment response and survival. The study group included 12 cases of MDS/MPN with 3q26.2 rearrangements detected by conventional karyotyping. There were 7 men and 5 women with a median age of 67 years (range, 51-79 years) at time of initial MDS/MPN diagnosis. Ten cases were classified as chronic myelomonocytic leukemia (CMML) and 2 were MDS/MPN, unclassifiable. Among CMML cases, 5 (50%) were proliferative type and 5 (50%) were dysplastic type. Based on blast counts, these 10 CMML were: CMML-0 (n = 2), CMML-1 (n = 3), and CMML-2 (n = 5). Eleven (92%) patients had 3q26 rearrangements at the initial diagnosis. Inv(3)(q21q26.2) was most common, identified in 7(58%) patients, followed by t(3;21)(q26.2;q22) in 2 patients and 1 patient each with t(3;3)(q21;q26.2), t(2;3)(p21;q26-27), and t(3;6)(q26.2;q26). Six (50%) patients had 3q26.2 rearrangements as a sole cytogenetic abnormality and 6 (50%) patients had additional cytogenetic abnormalities. Molecular studies revealed DNMT3A mutations in all 3 patients assessed and RAS mutations in 2 of 8 (25%) patients. No mutations in ASXL1 (n = 3), TET2 (n = 3), FLT3 ITD/D835 (n = 10), and CEBPA (n = 7) were detected. Most patients received hypomethylating agent based chemotherapy. The median follow-up was 11.5 months (range, 1.5-24 months) and at time of last follow-up, 11 (92%) died with a median survival of 13.4 months (range, 1.5-24 months). The only patient alive had a relatively short follow-up of 2.4 months and showed disease progression at the last visit. In conclusion, 3q26.2/EVI1 rearrangements are a rare event and usually present at time of initial diagnosis in MDS/MPN. The presence of 3q26.2/EVI1 rearrangements in MDS/MPN is associated with rapid disease progression, poor response to treatment, and a poor prognosis.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Hu Z,Hu S,Ji C,Tang Z,Thakral B,Loghavi S,Medeiros LJ,Wang Wdoi
10.1016/j.leukres.2017.12.004subject
Has Abstractpub_date
2018-02-01 00:00:00pages
25-28eissn
0145-2126issn
1873-5835pii
S0145-2126(17)30609-4journal_volume
65pub_type
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