Complete blood count differences in a cohort of Down syndrome neonates with transient abnormal myelopoiesis screened for GATA1 pathogenic variants.

Transient abnormal myelopoiesis (TAM) raises the risk for acute myeloid leukemia of Down syndrome (DS) (ML-DS), and both are related to GATA1 pathogenic variants. Here, we analyzed which findings on complete blood count (CBC) are associated with TAM in a cohort of neonates with DS screened for GATA1 pathogenic variants. The CBCs were compared among 70 newborns with DS, including 16 patients (22.9%) with TAM (cases), and 54 patients (77.1%) without TAM (controls). TAM was defined as peripheral circulating blasts (PCBs) ≥ 1%. PCR and direct sequencing were used to screen DNA samples from peripheral blood for GATA1 exon 2 mutations. Multivariate logistic regression analyses determined that the mean count of lymphocytes was significantly higher in DS infants with TAM (p = .035) and that lymphocytosis confers a risk for TAM (adjusted odds ratio = 7.23, 95% confidence intervals: 2.02-25.92). Pathogenic variants of GATA1 were identified in 2 of 70 analyzed DS neonates (2.9%), of which one had ML-DS and another had an asymptomatic TAM. Among those DS infants with TAM, the GATA1 pathogenic variant detection was 12.5%. Our results indicated that lymphocytosis is associated with TAM in neonates with DS. However, since not all infants with an abnormal CBC had TAM, and not all infants with TAM had GATA1 pathogenic variants, we emphasize that only the search for GATA1 pathogenic variants allows the proper identification of the subgroup of DS infants with a real increasing in risk for ML-DS.

Acute promyelocytic leukemia with PML/RARA (bcr1, bcr2 and bcr3) transcripts in a pediatric patient.

Patients with acute promyelocytic leukemia (APL) exhibit the t(15;17)(q24.1;q21.2) translocation that produces the promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion gene. Different PML breakpoints yield three alternative molecular transcripts, bcr1, bcr2 and bcr3. The present study reports the simultaneous presence of three PML/RARA transcripts in a pediatric female patient diagnosed with APL, according to the clinical characteristics, immunophenotype and karyotype of the patient. The simultaneous presence of the PML/RARA transcripts were detected using reverse transcription-quantitative PCR (RT-qPCR). This was confirmed with HemaVision-28N Multiplex RT-qPCR, HemaVision-28Q qualitative RT-qPCR and the AmpliSeq RNA Myeloid Panel. To the best of our knowledge, the pediatric patient described in the present study is the first case found to exhibit all three PML/RARA transcripts (bcr1, bcr2 and bcr3). Additionally, a microarray analysis was performed to determine the expression profile, potential predictive biomarkers and the implications of this uncommon finding. According to the information obtained from molecular monitoring, the results reported in the present study were associated with a good patient prognosis. In addition, upregulated genes that are rare in acute myeloid leukemia were identified, and these genes may be promising diagnostic biomarkers for further study. For example, CCL-1 is present in leukemic stem cells, causing treatment failure and relapse, and α- and ß-defensins have been reported exclusively in chronic myeloid leukemia. However, the results of the present study confirmed that they may also be present in APL. Thus, these findings suggested a possible signaling pathway that involves the PML/RARA oncoprotein in APL.

Case Report: Characterization of known (c.607G>C) and novel (c.416C>G) ELANE mutations in two Mexican families with congenital neutropenia.

The most common causes of congenital neutropenia are mutations in the ELANE (Elastase, Neutrophil Expressed) gene (19p13.3), mostly in exon 5 and the distal portion of exon 4, which result in different clinical phenotypes of neutropenia. Here, we report two pathogenic mutations in ELANE, namely, c.607G>C (p.Gly203Arg) and a novel variant c.416C>G (p.Pro139Arg), found in two Mexican families ascertained via patients with congenital neutropenia who responded positively to the granulocyte colony-stimulating factor (G-CSF) treatment. These findings highlight the usefulness of identifying variants in patients with inborn errors of immunity for early clinical management and the need to rule out mosaicism in noncarrier parents with more than one case in the family.

A translocation t(5;15)(q15;q11-13) infant case with acute lymphoblastic leukemia and literature review: prognosis implications.

Infant acute lymphoblastic leukemia (ALL) represents poor prognosis despite intensive chemotherapy. Rearrangements of chromosome 11q23 are not observed in 34% of the cases. Infant ALL patients with t(5;15)(p15;q11-13) are rare and sporadic. In large series of infant ALL studies, 6 patients have been reported. We present a new case of an infant ALL patient with t(5;15)(p15;q11-13), and a literature review. Considering the data provided by our case and previous reports, we reinforce that this chromosomal abnormality is characteristic of ALL patients under 12 months of age sharing break point in 5p15 and 15q11-13 and strengthen the existence of an infant ALL subgroup characterized by pre-B L1 ALL, CD10-positive, complete remission (100%), and event-free survival (71%), with a relatively good prognosis and clearly less severe than the 11q23 rearrangement cases. This abnormality can be considered a recurrent abnormality on this nosologic group.

Sweet Syndrome in an Adolescent Patient With Differentiation Syndrome Secondary to Promyelocytic Leukemia Treatment With All-Trans Retinoic Acid.

Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis that is histologically characterized by an infiltration of the dermis by neutrophils. A 12-year-old adolescent female patient recently diagnosed with acute promyelocytic leukemia presented with fever and was hospitalized for antibiotic management after 22 days of being treated with a treatment protocol based on daunorubicin, all-trans retinoic acid (ATRA), and prophylaxis with dexamethasone, the patient developed erythematous skin lesions located mostly on the extremities. Lesions evolved into painful subcutaneous nodules, and one lesion evolved into a 2.5-cm blister with a purple and necrotic base. A skin biopsy was performed and showed neutrophilic dermatosis which confirmed the diagnosis of SS. The patient's clinical features complied with criteria for differentiation syndrome complicated by shock. Two days after ATRA was suspended, the patient presented resolution of the fever and skin lesions. SS is a rare neutrophilic dermatosis secondary to an innate immune disorder classified into four categories: classical (idiopathic), para-inflammatory, paraneoplastic or pregnancy-related. SS has been described in patients with acute myeloid leukemia in adults secondary to the use of drugs such as ATRA or as a part of a paraneoplastic syndrome. SS can occur exceptionally in children with myeloid leukemia secondary to the use of drugs such as ATRA.