Crucial Role of BAALC-Expressing Progenitor Cells in Emergence and Development of Post-Transplantation Relapses in Patients with Acute Myeloid Leukemia

Abstract

This article presents data demonstrating frequent BAALC hyperexpression, also in combination with WT1 hyperexpression, in children and adults with acute myeloid leukemia (AML). Treatment included allogeneic hematopoietic stem cell transplantation. The analysis of serial measurements of BAALC and WT1 expression level in 50 AML patients (37 adults and 13 children) showed that the increased BAALC expression is more common in patients with M1, M2, M4, and M5 FAB variants of AML with equal frequency in adults and children. Furthermore, the increased BAALC expression was rather common in combination with the increased WT1 expression, which predicted poorer prognosis. Since BAALC expression level in AML patients is closely related to AMLproducing progenitor cells of leukemia hemato poiesis, a serial study of this phenomenon off ers insights into the role of these cells in emergence and development of post-transplantation relapses, which is of both theoretical and practical importance.

Near-Early T-Cell ALL with Overexpression of BAALC and BCL-2 Genes, Non-Responsive to High-Dose Chemotherapy and Hematopoietic Stem Cell Transplantation, but with Impressive Response to Venetoclax

“…As recently shown by our group [8][9][10], the level of BAALCexpression in patients with AML, measured by means of RT-qPCR, reflect the approximate numbers of BAALC-expressing Figure 2: Time course of molecular changes in patient with near-early T-ALL who was subjected to allo-HSCT from partially (9/10) matched nonrelative donor. The transplant was performed at relapse, with 77.5 % of blast cells in bone marrow and highly increased expression of BAALC (186%) and WT1 genes (9639 copies).…”

Quantitative study of BAALC- and WT1-expressing cell precursors in the patients with different cytogenetic and molecular AML variants treated with Gemtuzumab ozogamicin and hematopoietic stem cell transplantation

“…In our opinion, this phenomenon may be also explained by presence of active expression of WT1 gene by more mature precursors [12,15]. Confirmation of this hypothesis should extend our opportunities for evaluation of leukemic hematopoiesis on the level of leukemic precursors, using quantitative qRT-PCR [12,14,15]. To test this hypothesis, we performed parallel measurements of BAALC and WT1 expression levels in 14 AML patients with different cytological, cytogenetic and molecular variants of AML treated with combination of high-dose chemotherapy (ChT) and Mylotarg.…”

“…One line of evidence is based on some cases of acute promyelocytic leukemia (APL), where higher level of gene WT1 expression was coupled to lower blast cell numbers in bone marrow [12]. Moreover, this conclusion is also supported by similar discrepancy between higher WT1 gene expression and lower numbers of bone marrow blasts in 30% to 40% AML patients, both before and after HSCT [6,9,10,13,14]. In our opinion, this phenomenon may be also explained by presence of active expression of WT1 gene by more mature precursors [12,15].…”

BAALC-Expressing Earlier Leukemic Progenitors: Crucial Role in AML Relapses with Evaluation of Their Treatment and Prevention Efficacy

“…On the other hand, the data were obtained which presumed direct participation of ELP in selective expression of the BAALC gene [13,14]. On the basis of these data our hypothesis was drawn linking poor-risk BAALC overexpression directly with BAALCexpressing ELP [15][16][17] which can replace the older doubtful explanation of this phenomenon through BAALC-mRNA. If this explanation is true, then similar RT-qPCR might be used effectively in clinical setting for serial quantitative evaluation of BAALC-expressing ELP bulks.…”

“…In order to prove this concept, we have recently performed several closely tied projects. One of them [15] concerned of a crucial role of BAALC-expressing ELP in pathogenesis of relapses in both pediatric and adult AML, treated with hematopoietic stem cell transplantation (HSCT). The study enrolled 50 AML patients (37 adults and 13 children) who were treated by means of HSCT at Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation.…”