Genetic characteristics and treatment outcome in infants with KMT2A germline B-cell precursor acute lymphoblastic leukemia: Results of MLL-Baby protocol.

The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109 /L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulative incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.

Phylogeography of the striped field mouse (Apodemus agrarius Pallas, 1771) in light of new data from central part of Northern Eurasia.

A phylogeographic analysis of A. agrarius based on the complete mtDNA cytochrome b and control region sequences has been performed using data obtained for the first time for the species from large regions of the central part of Northern Eurasia (23 localities of Altai, Western Siberia, and the Urals). The obtained results have demonstrated a complex intraspecific differentiation of A. agrarius, which has manifested not only in the isolation of the isles populations in Southeast Asia (Jeju and Taiwan), but also in the genetic heterogeneity of mainland populations, which has reflected the history of the modern intraspecific genetic diversity formation against the background of changing physiographic conditions of Eurasia in the Quaternary. The divergence of genetic lineages has taken place apparently simultaneously (in mid-Pleistocene) on the territory of the Eastern part of the modern disjunctive range, where all the identified lineages are present today. The demographic history and possible evolutionary scenarios for A. agrarius in the Western part of the range have been considered. TMRC reconstructions have shown that the lifetime of the common ancestor of the lineage that expanded in the Western Palearctic is about 17.7 [95% HPD 13.2-22.5] kyr. This suggests that the transcontinental expansion of A. agrarius is a relatively recent event that has occurred after the LGM.