Sometimes it is better to wait: First Italian case of a newborn with transient abnormal myelopoiesis and a favorable prognosis

Abstract

Congenital leukemia is rare disease with an incidence of one to five cases per million births. Transient abnormal myelopoiesis (TAM), also called transient myeloproliferative disorder, is a pre-leukemia disorder that may occur in Down syndrome (DS) or non-DS infants. TAM may enter spontaneous remission; however, continual monitoring is required, as this disorder has been observed to develop into acute megakaryoblastic leukemia in 16–30% of cases. In the literature, 16 cases of TAM in non-DS infants have been reported. The case presented in the current study is, to the best of our knowledge, the first case of an Italian non-DS newborn presenting with clinical manifestations of acute leukemia at five days after birth, exhibiting a normal karyotype, trisomy 21 only in blast cells, and spontaneous remission. Chromosomal analyses on peripheral blood cells, bone marrow cells and dermal fibroblasts were conducted using a G-banding technique, and fluorescence in situ hybridization (FISH) was used to identify the critical regions of DS. Amplification of GATA binding protein 1 (GATA1) exon 2 genomic DNA was performed using polymerase chain reaction. Cytogenetic analysis of 50 peripheral blood cells and dermal fibroblasts from the patient revealed a normal karyotype: 46, XX. Conversely, cytogenetic analysis of the patient's bone marrow revealed an abnormal karyotype 47, XX+21. In order to investigate this result, FISH was performed, which identified the presence of three signals in 70% of the cells and two signals in 30% of bone marrow cells. GATA1 sequencing revealed the substitution of a single base (c.150delG) in exon 2. Seven months after the initial analysis, FISH and cytogenetic analyses of the stimulated/unstimulated peripheral blood cells and bone marrow cells were performed, revealing that each exhibited diploid signals, as observed in a normal karyotype.

Clinical, cytogenetic, and molecular analyses of 17 neonates with transient abnormal myelopoiesis and nonconstitutional trisomy 21

“…performed a literature review of 14 patients with TAM that was not associated with DS and reported that GATA1 mutations were analyzed in only eight patients, all of whom had GATA1 mutations as well as trisomy 21 in leukemic blasts, indicating that the biology of TAM without constitutional trisomy 21 was similar to that of TAM with constitutional trisomy 21/DS . After the report of Rozen et al., there have also been several case reports of TAM without constitutional trisomy 21 but harboring both trisomy 21 and GATA1 mutations in leukemic blasts . Here, we present the cytogenetic findings and GATA1 mutation status of a series of 17 patients with TAM and nonconstitutional trisomy 21 who had been tested for GATA1 mutations at a single institute.…”

“…19 After the report of Rozen et al, there have also been several case reports of TAM without constitutional trisomy 21 but harboring both trisomy 21 and GATA1 mutations in leukemic blasts. [21][22][23][24] Here, we present the cytogenetic findings and GATA1 mutation status of a series of 17 patients with TAM and nonconstitutional trisomy 21 who had been tested for GATA1 mutations at a single institute. All 17 patients harbored both trisomy 21 and GATA1 mutations in leukemic blasts, clearly showing that the molecular pathogenesis is common between TAM with and without constitutional trisomy 21.…”

Congenital leukemia: A case report and review of literature

“…A “watch and wait” approach with careful monitoring (including frequent physical examinations and blood counts) is necessary for CL with stable illness, because there is a possibility of SR without the use of chemotherapeutic medications that are associated with adverse effects[ 10 , 37 ]. According to the newly released guidelines, a low-dose cytarabine therapy is recommended for cases with multiorgan failure, high WBC counts (> 100 × 10 9 /L), hepatopathy, and other life-threatening diseases.…”

Síndrome Mieloproliferativo Transitorio asociado a Síndrome de Down e Hidrops Fetal: Reporte de caso

“…El gen GATA-1 es considerado como factor de riesgo de evolución a leucemia aguda, mientras que una leucocitosis superior a 100 000mm3, hepatomegalia e ictericia están directamente relacionados a mayor riesgo de mortalidad [20]. La adecuada evolución clínica y del recuento leucocitario del paciente descartó la presencia de una leucemia aguda congénita y soportan el diagnóstico de SMT; aunque en este paciente no se pudo realizar el estudio de la mutación (GATA-1).…”