Contributions
Abstract: PB1411
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
We report a female patient of Armenian origin initially suspected with myelodysplastic syndrome of unknown origin at the age of 8 y.o based on initial analysis of the bone marrow described also with abnormal hemoglobin, anemia and neutropenia. However, the clinical picture was also characterized with periodic fevers accompanied with joint and thoracic pains starting from the age 5 y.o. Later, the patient was described with splenomegaly and hepatomegaly. No familial case was reported. Further, she developed a swelling of the feet with pain, exudative pneumonia, general weakness and loss of weight.Aims
The lack of clinical diagnosis for treatment required performance of the differential complex examinations, including the cellular immunophenotyping, cytogenetic, and whole genome analyses.
Methods
The analysis of human cluster of differentiation (CD) antigens the patient’s bone marrow was analyzed by flow cytometry analysis capturing 30 human CDs. Molecular cytogenetic analysis was performed by FISH method on the patient’s bone marrow cells for the detection of the major seven cytogenetic aberrations related to leukemias. Whole Exome Sequencing (WES) of the patient’s DNA extracted from the peripheric leukocytes on a MiSeq platform.
Results
Immunophenotyping analysis detected less than 7% of blast cells in the bone marrow which antigen spectrum (CD7, CD11a, CD11c, CD13, CD33, CD34, CD45, CD64, CD117, CD123, and HLA-DR) confirmed its relation to acute myeloid leukemia. Molecular cytogenetic analysis did not find any cytogenetic aberration in the bone marrow. However, the WES detected two pathogenic variants in two genes: a heterozygous variant c.214G>A (p.Ala72Thr) in the PTPN11 gene which is associated with developmental and lymphatic dysplasia and a heterozygous variant c.2080A>G (p.Met694Val) in the MEFV gene which is associated to hereditary autoinflammatory syndromes. De novo status of the detected PTPN11 variant was confirmed by parental testing. Detection of the heterozygous state of the PTPN11 variant with frequency of 40% is compatible with both germline and mosaic states.
Conclusion
The WES result was compatible with a genetic diagnosis of the autosomal-dominant Noonan syndrome type 1 and/or the predisposition to juvenile myelomonocytic leukemia caused by somatic PTPN11 variants. Further physical examination of the patient did describe several features characteristic to the Noonan syndrome, including the short stature, chest abnormality, hypertelorism, as well as facial and developmental features of variable degree. Pathogenic somatic variants in the PTPN11 gene are associated with juvenile myelomonocytic leukemia. Leukemias occurring in the absence of any other finding of Noonan syndrome could harbor somatic PTPN11 variants, particularly in children with myelodysplastic syndrome. The latter is indeed more specific in case of excess of blast cells in acute myeloid leukemia with poor prognosis. Therefore, more detailed physical and phenotypic characterization of the patient at the initial state of the disease could support to the suspicion of the rare genetic syndrome of DNA reparation system associated with oncological features. The heterozygous MEFV pathogenic variant common in the Armenian population is the strongest pathogenic variant in patients with Familial Mediterranean Fever (FMF). Despite FMF is an autosomal recessive disorder, less than 10% of cases are described with only one MEFV mutation. Thus, several clinical features of the patient not specific to the myelomonocytic leukemia are explained with accompanied autoinflammatory condition.
Keyword(s):
Abstract: PB1411
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
We report a female patient of Armenian origin initially suspected with myelodysplastic syndrome of unknown origin at the age of 8 y.o based on initial analysis of the bone marrow described also with abnormal hemoglobin, anemia and neutropenia. However, the clinical picture was also characterized with periodic fevers accompanied with joint and thoracic pains starting from the age 5 y.o. Later, the patient was described with splenomegaly and hepatomegaly. No familial case was reported. Further, she developed a swelling of the feet with pain, exudative pneumonia, general weakness and loss of weight.Aims
The lack of clinical diagnosis for treatment required performance of the differential complex examinations, including the cellular immunophenotyping, cytogenetic, and whole genome analyses.
Methods
The analysis of human cluster of differentiation (CD) antigens the patient’s bone marrow was analyzed by flow cytometry analysis capturing 30 human CDs. Molecular cytogenetic analysis was performed by FISH method on the patient’s bone marrow cells for the detection of the major seven cytogenetic aberrations related to leukemias. Whole Exome Sequencing (WES) of the patient’s DNA extracted from the peripheric leukocytes on a MiSeq platform.
Results
Immunophenotyping analysis detected less than 7% of blast cells in the bone marrow which antigen spectrum (CD7, CD11a, CD11c, CD13, CD33, CD34, CD45, CD64, CD117, CD123, and HLA-DR) confirmed its relation to acute myeloid leukemia. Molecular cytogenetic analysis did not find any cytogenetic aberration in the bone marrow. However, the WES detected two pathogenic variants in two genes: a heterozygous variant c.214G>A (p.Ala72Thr) in the PTPN11 gene which is associated with developmental and lymphatic dysplasia and a heterozygous variant c.2080A>G (p.Met694Val) in the MEFV gene which is associated to hereditary autoinflammatory syndromes. De novo status of the detected PTPN11 variant was confirmed by parental testing. Detection of the heterozygous state of the PTPN11 variant with frequency of 40% is compatible with both germline and mosaic states.
Conclusion
The WES result was compatible with a genetic diagnosis of the autosomal-dominant Noonan syndrome type 1 and/or the predisposition to juvenile myelomonocytic leukemia caused by somatic PTPN11 variants. Further physical examination of the patient did describe several features characteristic to the Noonan syndrome, including the short stature, chest abnormality, hypertelorism, as well as facial and developmental features of variable degree. Pathogenic somatic variants in the PTPN11 gene are associated with juvenile myelomonocytic leukemia. Leukemias occurring in the absence of any other finding of Noonan syndrome could harbor somatic PTPN11 variants, particularly in children with myelodysplastic syndrome. The latter is indeed more specific in case of excess of blast cells in acute myeloid leukemia with poor prognosis. Therefore, more detailed physical and phenotypic characterization of the patient at the initial state of the disease could support to the suspicion of the rare genetic syndrome of DNA reparation system associated with oncological features. The heterozygous MEFV pathogenic variant common in the Armenian population is the strongest pathogenic variant in patients with Familial Mediterranean Fever (FMF). Despite FMF is an autosomal recessive disorder, less than 10% of cases are described with only one MEFV mutation. Thus, several clinical features of the patient not specific to the myelomonocytic leukemia are explained with accompanied autoinflammatory condition.
Keyword(s):