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TP53 alteration in chronic lymphocytic leukemia indicates a high-risk disease that is usually refractory to chemotherapy. It may be caused by deletion of 17p involving the loss of TP53 gene, which occurs in low percentage of patients at diagnosis but can be acquired as the disease progresses. Since patients may harbor TP53 mutation without chromosome 17p deletion, consensus recommendations call for both cytogenetic and PCR mutation analysis of TP53 in chronic lymphocytic leukemia. We conducted a single-institution retrospective study to investigate the clinicopathologic features of chronic lymphocytic leukemia with TP53 alterations as well as the utility of different diagnostic modalities to identify p53 alterations. Forty percent of chronic lymphocytic leukemia patients with TP53 alterations demonstrated atypical lymphocytes with cleaved/irregularly shaped nuclei and/or large atypical lymphoid cells with abundant cytoplasm in the peripheral blood. Progression was also observed in lymph node and bone marrow samples (21% with Richter transformation; 33% with findings suggestive of “accelerated phase” of chronic lymphocytic leukemia including prominent proliferation centers and/or increased numbers of prolymphocytes). However, the presence of the morphologic features suggestive of “accelerated phase” had no effect on overall survival within the chronic lymphocytic leukemia group with TP53 abnormalities (p > 0.05). As previously reported by others, a subset of patients with TP53 alterations were only identified by either PCR mutation analysis (12%) or cytogenetic studies (14%). p53 immunostain positivity was only identified in approximately half of the patients with TP53 alterations identified by either method, and it failed to identify any additional patients with p53 abnormalities. In summary, chronic lymphocytic leukemia patients with TP53 alterations frequently show atypical morphologic features. Use of multiple modalities to identify p53 abnormalities is recommended to ensure optimal sensitivity and specificity.

The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. We retrospectively identified patients with ≥50% erythroid precursors and either ≥20% bone marrow blasts or ≥20% peripheral blood blasts at the time of initial diagnosis at seven major academic centers. Laboratory and clinical data were obtained. Patients were then reclassified according to 2016 WHO guidelines. A matched control group was also obtained. We identified 146 patients with acute myeloid leukemia with erythroid predominance (62% M, average age: 62 y, range: 5-93 y). Of these, 91 were acute myeloid leukemia with myelodysplasia-related changes, 20 (14%) were therapy-related myeloid neoplasm, 23 (16%) acute myeloid leukemia, not otherwise specified, and ten acute myeloid leukemia with recurrent cytogenetic/molecular abnormalities. The bone marrow blast count ranged from 9-41%. There was no difference in survival for patients with erythroid predominance compared to patients with acute myeloid leukemia without erythroid proliferations. In a multivariable analysis, cytogenetic risk was the only significant predictor of survival. We find a significantly lower rate of FLT3 and RAS pathway alterations in acute myeloid leukemia with erythroid predominance compared to controls. Our study is one of the first to apply the 2016 WHO guidelines for classification of acute myeloid leukemia. We find acute myeloid leukemia with erythroid predominance is a heterogeneous group and that erythroid richness has no impact on overall survival.