High Incidence of IDH Mutations in Acute Myeloid Leukemia with Cup-Like Nuclei.
Dinesh Rakheja, Robert Collins, Mu Su, Midori Mitui, Nitin J Karandikar, Weina Chen. UT Southwestern Medical Center, Dallas, TX
Background: Somatic mutations of IDH1 and IDH2 have recently been described in acute myeloid leukemia (AML) with an incidence of 10-20%. These mutations are clustered in AML with normal karyotype and NPM1 mutations. This study aimed to further define the clinicopathologic, immunophenotypic and genetic features of AML with such mutations.
Design: Genomic DNA of 14 AML cases was extracted from paraffin-embedded bone marrow blocks or leftover samples from flow cytometry (FC) laboratory. Exon 4 of IDH1 and exon 4 of IDH2 were sequenced. Immunophentoypic analysis was performed by 4-color FC.
Results: There were 6 IDH-mutated cases (age 41-59 years, 3 females and 3 males) and 8 IDH-wild type cases (age 1-73 years, 4 females and 4 males). There were no age and gender differences between the two groups. Two patients had IDH1 mutations, and 4 had IDH2 mutations. Compared to IDH-wild type cases, IDH-mutated cases had a higher frequency of AML morphology without maturation and with cup-like nuclei (5/6 vs 1/8), a trend towards normal cytogenetics (6/6 vs 3/6), and lack of both CD34 and HLA-DR (5/6 vs 3/8). Of 3 cases of AML with cup-like nuclei tested for NPM1 and FLT3 mutations, all were positive for NPM1 mutation and 1 for FLT3-ITD mutation. Expression profiles for the following markers by FC were similar in the two groups (positive/tested cases in 2 groups): CD7 (2/14), CD11b(4/12), CD13(10/14), CD15(9/14), CD33(14/14), CD56(4/14), CD64(5/14), CD117(12/14), MPO (9/11), and Tdt (1/12).
Conclusions: Our studies show that AML with cup-like nuclei, which is characterized by normal cytogenetics, NPM1 and FLT3 mutations, and lack of CD34/HLA-DR, has a much higher incidence of IDH mutations (83%) than the overall incidence of IDH mutations in AML. These results suggest that AML with cup-like nuclei may be genetically distinct, a hypothesis that needs to be tested/validated in future studies.
Monday, February 28, 2011 1:00 PM
Poster Session II # 194, Monday Afternoon