There is evidence that relapses of acute myeloid leukemia (AML) are closely related to heterogeneous population of leukemic precursors. At least, two classes of the leukemia-initiating cells (LIC) may be discerned, according to recent experimental studies with hematopoietic cell transplants to immunodeficient mice. The main class of LICs is presented by immature precursors with CD34 + CD38immunophenotype which, in turn, are capable of selective expression of BAALC gene. The second class of LICs is presented by relatively mature precursors with more differentiated immunophenotypes. According to indirect findings, they are able of WT1 gene expression, along with blast cells. Since both BAALC and WT1 mRNAs may be quantitatively evaluated by means of standardized quantitative polymerase reaction in real time (qRT-PCR), this approach may be effective for specifying the mechanisms of relapses and resistance to therapy in AML patients. The aim of this work was to perform simultaneous dynamic evaluation of BAALC and WT1 genes expressions along with determination of blast numbers in the tested bone marrow samples in 14 AML patients treated at our Center with Gemtuzumab ozogamicin (GO, Mylotarg), which was combined with high-dose chemotherapy (ChT), followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our preliminary results are as follows: a) superior 3-year overall survival (OS) in general group of patients with normal or nearly-normal karyotypes, and FLT3-mutated AML variants as compared to those with more complex karyotypes and EVI1 gene overexpression (85.7% vs 16.7%; p=0.032); b) highly sensitive response of immature BAALC-expressing precursors to combined ChT and GO treatment; c) hypothetical participation of some mature precursors, along with blast cells, in WT1 gene expression; d) real evidence for switching hematopoietic regulation from immature BAALC-expressing precursors to more mature WT1-expressing progeny. These results suggest diagnostic utility of combined BAALC/ WT1/blast counts panel for quantitative studies and assessment of distinct precursors in AML progression and emergence of relapses.

The study assessed the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 34 patients with cytogenetically verified variants of myelodysplastic syndrome (MDS) with trisomy 8 and/or monosomy 7, who were treated at the RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation from 2013 to 2020. Both adult and pediatric MDS were analyzed without excluding the variants with two additional chromosomal abnormalities or complex karyotype. The study revealed that а) allo-HSCT should be performed in the treatment of both MDS variants; b) the outcomes of trisomy 8 treatment appeared to be better; c) children with monosomy 7 showed a higher rate of toxic complications in allo-HSCT.

The present review provides the analysis of theoretical background and therapy of prognostically poorest EV/1-positive myeloid leukemias and myelodysplastic syndromes which is performed at the RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation. The focus is on the evidence of the dominating role of EV/1 gene in impaired epigenetic regulation of hematopoiesis and, thus, on the feasibility of allogeneic hematopoietic stem cell transplantation with hypomethylating agents and/ or trans-retinoic acid used for these diseases treatment.

The present paper provides evidence for a high detection rate of BAALC gene overexpression, also combined with WT1 gene overexpression, in patients with myelodysplastic syndromes (MDS) and FISH-verified chromosome defects. The BAALC and WT1 gene expression profiling of 16 MDS patients (6 out of them received allogeneic hematopoietic stem cell transplantation) showed an increased BAALC expression in 14 patients. The expression level in 2 patients was near the cut-off. Low expression levels were identified in a female patient with isolated 5q deletion in karyotype and also with its combination with complex karyotype. On the other hand, the highest expression levels were reported in patients with normal karyotype and 3q26 locus rearrangement, which was associated with EVI1 gene overexpression. Since the BAALC expression level, at least in patients with the major (except for М3 and М7) FAB-variants of acute myeloid leukemias (AML), was closely associated with BAALC-producing precursor cells of leukemia clone, a profound study of this phenomenon in MDS patients seems to be important for understanding the finest mechanisms underlying the pathogenesis of AML and AML relapses on the level of precursor cells.