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Published on: November 5, 2019
[Immunophenotypic and clinical characteristic analysis of NPM1 mutated acute myeloid leukemia with a normal
Yan-Rong Liu1, Yue-Yun Lai1, Yan Chang1
1Institute of Hematology, People's Hospital of Peking University, Beijing 100044, China.
Insights
NPM1 mutated acute myeloid leukemia (AML) with normal karyotype shows distinct immunophenotypes, including lower early differentiation antigens and better treatment response compared to NPM1-negative AML. These findings aid in refining AML classification and treatment strategies.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Acute myeloid leukemia (AML) is a heterogeneous malignancy.
- NPM1 gene mutations are common in AML, particularly in cases with a normal karyotype.
- Understanding the immunophenotypic and clinical characteristics of NPM1-mutated AML is crucial for diagnosis and treatment.
Purpose of the Study:
- To compare immunophenotypic and clinical features of NPM1-mutated AML with normal karyotype (NPM1m(+)AML) against NPM1-unmutated AML with normal karyotype (NPM1m(-)AML).
- To analyze differences within NPM1m(+)AML based on French-American-British (FAB) subtypes (M1/2 vs. M4/5).
Main Methods:
- Multiparameter flow cytometry was used for immunophenotyping and detection of NPM1 mutations.
- Real-time RT-PCR or PCR identified NPM1 gene mutation types (A, B, D) and other leukemic fusion genes.
- 77 NPM1m(+)AML patients and 55 NPM1m(-)AML patients with normal karyotype were analyzed.
Main Results:
- Significant differences were observed between NPM1m(+)AML and NPM1m(-)AML in sex, white blood cell count, platelet count, blast percentage, WT1 expression, FLT3-ITD mutation rate, and treatment response.
- NPM1m(+)AML exhibited lower expression of early differentiation antigens (CD34, HLA-DR, CD117, CD38) and lymphocytic antigens (CD7, CD4, CD19, CD2), with higher expression of CD33 and CD123.
- Within NPM1m(+)AML, M4/5 subtypes showed higher expression of monocytic differentiation antigens (HLA-DR, CD7) and lower CD117 expression compared to M1/2 subtypes.
Conclusions:
- NPM1-mutated AML with normal karyotype has a distinct immunophenotype characterized by reduced early differentiation and lymphoid markers, and increased CD33/CD123 expression.
- NPM1m(+)AML patients demonstrate a higher WT1 expression level and a better response to treatment.
- Monocytic differentiation markers are specifically upregulated in M4/5 subtypes within the NPM1m(+)AML group.
Abstract:
This study was purposed to compare the immunophenotypic and clinical characteristics of NPM1 mutated acute myeloid leukemia with a normal karyotype under the similar constituent ratio of FAB subtypes. Immunophenotyping and NPM1 gene mutation type-A,B and D and other leukemic related fusion genes were detected by multiparameter flow cytometry and real time RT-PCR or PCR, respectively. 77 AML patients with a normal karyotype (NK) and mutated NPM1 gene (NPM1m(+)AML) detected by immunophenotyping assay were included in this study. 55 cases without NPM1 mutation (NPM1m(-)AML) and with normal karyotype were served as negative control. The results showed that there was significant difference between NPM1m(+)AML and NPM1m(-)AML in terms of sex, white blood count, platelet counts, blast, WT1 expression level, FLT3-ITD mutation positive rate and response to treatment. The characteristic immunophenotype is lower expression of early differentiation-associated antigens (CD34, HLA-DR, CD117, CD38), lymphocytic antigens (CD7, CD4, CD19, CD2) and higher expression of CD33 and CD123 (P < 0.05). When above features was further analyzed between the M1/2 and M4/5 subgroups in NPM1m(+)AML patients, the M1/2 cases retained a higher frequency in women and a higher WT1 expression level (P < 0.05) . Monocytic differentiation-associated antigens including HLA-DR and lymphocytic antigens CD7 were higher expressed and CD117 was lower expressed in M4/5 subgroup (P < 0.05). It is concluded that under condition of similar constituent ratio of M1/2 and M4/5 subtype and normal karyotype, NPM1m(+)AML patients have higher WT1 expression level and better response to treatment. The major immunophenotype features of NPM1m(+)AML patients are lower expression of early differentiation antigens and lymphoid lineage antigens and higher expression of CD33 and CD123. Monocytic differentiation-associated antigens only higher are expressed in M4/5 cases when compared with M1/2 cases within NPM1m(+) AML patients.
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