Detection of Mono/Oligo Clonal IgH Gene Rearrangements and Characterization of Associated Clinicopathologic Features in Acute Myeloid Leukemia
X Qiu, P Lin, X Sun, J You, LJ Medeiros, CC Yin. MD Anderson Cancer Center, Houston, TX
Background: It has been shown that immunoglobulin heavy chain (IgH) gene rearrangements, a function of B-cells and plasma cells, can be detected in non-B-cell malignancies including acute myeloid leukemia (AML). However, the clinicopathologic features of this subset of AML has not been studied.
Design: We assessed IgH gene rearrangements by PCR using V and J consensus primers followed by genescan in 105 AML cases. We also evaluated IgH and Ig kappa light chain (IgK) gene expression in six AML cell lines (HEL, HL-60, KG-1, NB-4, THP-1, OCI-AML3) by RT-PCR, Western blot and immunohistochemistry.
Results: Monoclonal and oligoclonal IgH gene rearrangements each was detected in four cases, accounting for 7.6% of total cases. There were five men and three woman (age, 33-82 years, median, 68). The leukemias were classified as acute myelomonocytic leukemia (M4, n=5), AML with t(8;21) (n=1), AML arising from myelodysplastic syndrome (AML/MDS, n=1), and therapy-related AML (n=1). Multilineage dysplasia was observed in all cases. Immunophenotyping showed that the blasts were uniformly positive for CD13, CD33, CD34, CD38, CD117, HLA-DR, and myeloperoxidase; CD14 and CD64 were also expressed by the M4 cases. No lymphoid marker was expressed except for CD19 by the case with t(8;21). Six cases had diploid karyotype. The AML/MDS showed del(7q) and del(20q). The other showed t(8;21)(q22;q22). Five cases were positive for Flt-3 internal tandem duplication (ITD). One was positive for Ras mutation. All patients received chemotherapy. With a median follow-up of 8 months (range, 1-22 months), five died of disease, one had persistent AML, the one with t(8;21) was in clinical remission with low-level disease detected by RT-PCR. One patient was lost to follow-up. Studies with six AML cell lines revealed that IgH gene transcripts were expressed in HEL, KG-1, THP-1, OCI-AML3, and IgK gene transcripts were detected in all. This was further confirmed by Western blot and immunocytochemistry.
Conclusions: Mono/oligo clonal IgH gene rearrangements is present in a subset of AML. These cases often demonstrate myelomonocytic differentiation, multilineage dysplasia, diploid karyotype, higher frequency of Flt-3 mutation, poor clinical outcome, and is not associated with lymphoid marker expression. Further study to evaluate the characteristics and function of the rearranged IgH gene is warranted to explore its implications in the pathogenesis, detection of minimal residual disease, as well as targeted therapy of AML.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 181, Wednesday Afternoon