PMC9378963_01
Case report timeline. ALL, acute lymphoblastic leukemia; PID, primary immunodeficiency.
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The timeline of case report is shown in Figure 1. Bone marrow smear showed normal did not present morphologic abnormalities (Supplementary Figure 1), and all cell lineages were represented and their proportions were appropriate for age (Supplementary Table 2). BM MRD immunophenotyping confirmed BCP-ALL remission with a balanced distribution of myeloid cells (46.8% of total cells, mostly neutrophils at different stages of maturation) and erythroid cells (total of 41.4%).
(A) Distribution of whole blood leukocyte subsets was based on differential expression of CD45 and side scatter characteristics: lymphocytes (low scatter and high CD45 expression), monocytes (medium side scatter and CD45 expression), and polymorphonuclears (high scatter and low CD45 expression) composed 19.0, 1.2% and CD79.8% of whole blood leukocytes, respectively. T lymphocytes were defined as CD3+CD19- cells, B lymphocytes as CD19+CD3- cells and composed 98.7% and 0.08% of total lymphocyte population, respectively. NK cells defined as CD3-CD16.CD56+ cells composed 1.1% of whole lymphocyte population.(B) T lymphocyte gate was set up based on high CD3 expression and low side scatter. Within T cell gate two subsets were identified: T helper (CD3+CD4+) and T suppressor (CD3+CD8+) cells. Recent thymic emigrants were identified as CD31+CD45RA+, while regulatory T cells as CD25+CD127- within T helper cell population. Remaining T lymphocyte maturation stages: naive (CD27+CD45RO-), memory (CD27+CD45RO+), effector memory (CD27-CD45RO+) and effector (CD27-CD45RO-) were defined in the similar way within T helper (CD3+CD4+) and T suppressor (CD3+CD8+) gates. Distribution of T cell receptor variants was defined based on TCRalphabeta and TCRgammadelta expression within T cell gate).
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T lymphocyte production, minor defects in T cell maturation, and absence of TCRgammadelta+ T-cells (Figure 2). The values of the lymphocyte subpopulations with age-adjusted normal ranges are shown in Table 1. During 12 months of posttransplant observation, the patient showed both BM recovery and immune reconstitution (Supplementary Figure 2), and did not manifest any infectious or non-infectious complications; in particular, she remained free from symptoms of acute or chronic graft-versus-host disease, and thus immunosuppressive treatment was successfully stopped.
Genetic testing of the proband's family. (A) A pedigree of the proband's family. The proband with BCP-ALL had a germline mutation in exon 5 of the GATA2 gene (c.1047T>G, Cys349Trp) inherited from her father with MDS. (+) denotes heterozygous mutation carrier in the germline; (-) denotes wild-type in the germline. A diagonal line through a symbol indicates that the person is deceased (B) Chromatograms of germline GATA2 variant in the proband, and proband's parents and sister.
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Two paternal aunts died of breast and colon cancer, and one maternal aunt developed breast cancer (Figure 3A). This mutation was also found in the symptomatic father, but was absent in healthy mother and sisters (Figure 3B).
Flow cytometry dot-plots representing the lymphoid, monoid and immature precursor cell subsets in the examined bone marrow sample. Lymphoid subset was represented mostly by T-cells and NK-cells. No mature B-cells nor precursor B-cells were present. Monoid lineage was represented mainly by mature monocytes (84.0% of CD14+); 8% of monocytes were CD56+.
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Lymphoid, myeloid, and immature precursor cell subsets comprised 8.4%, 0.49%, and 0.58% of the total cells, respectively (Figure 4).