Contributions
Abstract: PB2271
Type: Publication Only
Background
Juvenile myelomonocytic leukemia (JMML) is a rare clonal myelodysplastic/myeloproliferative neoplasm that occurs in infancy and early childhood, characterized by persistent monocytosis, no Philedelphia chromosome or BCR-ABL1 fusion gene, less than 20% myelo-monoblasts in the marrow and granulocyte-macrophage colony-stimulating factor hypersensitivity among other diagnostic criteria. The median age at presentation is 2 years (range 0.1-11.4) with an incidence of 1.2 per million child per year.
Clinical and laboratory diagnostic criteria for JMML have recently incorporated molecular genetic analyses in the form of somatic and/or germline mutations in canonical RAS pathway genes (e.g., PTPN11, NF1, NRAS, KRAS, and CBL).
Aims
We sought to unravel a comprehensive genetic picture using clinical exome sequencing in an 18-month-old Saudi female child from a non-consanguineous marriage who presented with a JMML pathology and showed hematogones with 1% myeloblasts by flow cytometry.
Methods
Diagnostic work-up included pathology including cytomorphology, multicolour flow cytometry, chromosomal and FISH analyses, and array CGH for duplication and deletion analyses. For unraveling genetic etiology, exome sequencing was performed.
Results
Cytomorphology and radiology revealed JMML pathology with hepatosplenomegaly. Immunophenotyping of bone marrow lymphocytes by flow cytometry revealed hematogones with 1% myeloblasts positive for CD34, CD33 and CD13. Multicolour flow revealed T, B and NK lymphocytosis with intact expression of MHC classII antigens on B-cells, 12.6% activated T-cells (CD3+DR+) and intact expression of adhesion molecules. Chromosomal analyses revealed a normal female karyotype with no apparent numerical or structural abnormalities, and FISH analyses for comprehensive AML panel was normal. Deletion and duplication analyses of the Rasopathy panel genes vias aCGH revealed negative results. However, clinical exome sequencing in this patient revealed homozygous and/or heterozygous mutations in canonical RAS pathway genes in addition to gene variants related to acute myeloid leukemia.
Conclusion
This is a first report from Saudi Arabia and a second only report in the literature using clinical exome sequencing in JMML showing homozygous mutaion in the rasopathy gene CBL and suggests that exome sequencing holds great promise as a diagnostic tool in these patients who have the potential to transform to AML and therefore may warrants quick clinical intervention.
Session topic: 15. Myeloproliferative neoplasms – Biology & Translational Research
Keyword(s): JMML
Abstract: PB2271
Type: Publication Only
Background
Juvenile myelomonocytic leukemia (JMML) is a rare clonal myelodysplastic/myeloproliferative neoplasm that occurs in infancy and early childhood, characterized by persistent monocytosis, no Philedelphia chromosome or BCR-ABL1 fusion gene, less than 20% myelo-monoblasts in the marrow and granulocyte-macrophage colony-stimulating factor hypersensitivity among other diagnostic criteria. The median age at presentation is 2 years (range 0.1-11.4) with an incidence of 1.2 per million child per year.
Clinical and laboratory diagnostic criteria for JMML have recently incorporated molecular genetic analyses in the form of somatic and/or germline mutations in canonical RAS pathway genes (e.g., PTPN11, NF1, NRAS, KRAS, and CBL).
Aims
We sought to unravel a comprehensive genetic picture using clinical exome sequencing in an 18-month-old Saudi female child from a non-consanguineous marriage who presented with a JMML pathology and showed hematogones with 1% myeloblasts by flow cytometry.
Methods
Diagnostic work-up included pathology including cytomorphology, multicolour flow cytometry, chromosomal and FISH analyses, and array CGH for duplication and deletion analyses. For unraveling genetic etiology, exome sequencing was performed.
Results
Cytomorphology and radiology revealed JMML pathology with hepatosplenomegaly. Immunophenotyping of bone marrow lymphocytes by flow cytometry revealed hematogones with 1% myeloblasts positive for CD34, CD33 and CD13. Multicolour flow revealed T, B and NK lymphocytosis with intact expression of MHC classII antigens on B-cells, 12.6% activated T-cells (CD3+DR+) and intact expression of adhesion molecules. Chromosomal analyses revealed a normal female karyotype with no apparent numerical or structural abnormalities, and FISH analyses for comprehensive AML panel was normal. Deletion and duplication analyses of the Rasopathy panel genes vias aCGH revealed negative results. However, clinical exome sequencing in this patient revealed homozygous and/or heterozygous mutations in canonical RAS pathway genes in addition to gene variants related to acute myeloid leukemia.
Conclusion
This is a first report from Saudi Arabia and a second only report in the literature using clinical exome sequencing in JMML showing homozygous mutaion in the rasopathy gene CBL and suggests that exome sequencing holds great promise as a diagnostic tool in these patients who have the potential to transform to AML and therefore may warrants quick clinical intervention.
Session topic: 15. Myeloproliferative neoplasms – Biology & Translational Research
Keyword(s): JMML