Increased gene expression in human promyeloid leukemia cells exposed to trans,trans-muconaldehyde, a hematotoxic benzene metabolite

Abstract T-cell lymphoblastic lymphoma (T-LBL) and lymphoblastic leukemia (T-ALL) represent malignancies that arise from the transformation of immature precursor T cells. Similarities in T-LBL and T-ALL have raised the question whether these entities represent 1 disease or reflect 2 different diseases. The genetic profiles of T-ALL have been thoroughly investigated over the last 2 decades, whereas fairly little is known about genetic driver mutations in T-LBL. Nevertheless, the comparison of clinical, immunophenotypic, and molecular observations from independent T-LBL and T-ALL studies lent strength to the theory that T-LBL and T-ALL reflect different presentations of the same disease. Alternatively, T-LBL and T-ALL may simultaneously evolve from a common malignant precursor cell, each having their own specific pathogenic requirements or cellular dependencies that differ among stroma-embedded blasts in lymphoid tissues compared with solitary leukemia cells. This review aims to cluster recent findings with regard to clinical presentation, genetic predisposition, and the acquisition of additional mutations that may give rise to differences in gene expression signatures among T-LBL and T-ALL patients. Improved insight in T-LBL in relation to T-ALL may further help to apply confirmed T-ALL therapies to T-LBL patients.

Download Full-text

Pectenotoxin-2 represses telomerase activity in human leukemia cells through suppression of hTERT gene expression and Akt-dependent hTERT phosphorylation

FEBS Letters ◽

10.1016/j.febslet.2008.08.030 ◽

2008 ◽

Vol 582 (23-24) ◽

pp. 3263-3269 ◽

Cited By ~ 14

Author(s):

Mun-Ock Kim ◽

Dong-Oh Moon ◽

Sang-Hyuck Kang ◽

Moon-Soo Heo ◽

Yung Hyun Choi ◽

...

Keyword(s):

Gene Expression ◽

Telomerase Activity ◽

Leukemia Cells ◽

Human Leukemia ◽

Htert Gene ◽

Human Leukemia Cells ◽

Pectenotoxin 2

Download Full-text

Differential gene expression in acute lymphoblastic leukemia cells surviving allogeneic transplant

Cancer Immunology Immunotherapy ◽

10.1007/s00262-010-0889-y ◽

2010 ◽

Vol 59 (11) ◽

pp. 1633-1644 ◽

Cited By ~ 3

Author(s):

Jessica C. Shand ◽

Johan Jansson ◽

Yu-Chiao Hsu ◽

Andrew Campbell ◽

Craig A. Mullen

Keyword(s):

Gene Expression ◽

Acute Lymphoblastic Leukemia ◽

Differential Gene Expression ◽

Lymphoblastic Leukemia ◽

Leukemia Cells ◽

Allogeneic Transplant ◽

Differential Gene

Download Full-text

Control of globin gene expression by steroid hormones in differentiating friend leukemia cells

Cell ◽

10.1016/0092-8674(78)90014-4 ◽

1978 ◽

Vol 15 (2) ◽

pp. 447-453 ◽

Cited By ~ 51

Author(s):

Shyh-Ching Lo ◽

Rebecca Aft ◽

Jeffrey Ross ◽

Gerald C. Mueller

Keyword(s):

Gene Expression ◽

Steroid Hormones ◽

Globin Gene ◽

Leukemia Cells ◽

Friend Leukemia ◽

Globin Gene Expression

Download Full-text

Folate Pathway Gene Expression Differs in Genetic Subtypes of Acute Lymphoblastic Leukemia and Influences Methotrexate Pharmacodynamics.

Blood ◽

10.1182/blood.v104.11.452.452 ◽

2004 ◽

Vol 104 (11) ◽

pp. 452-452

Author(s):

Leo Kager ◽

Meyling H. Cheok ◽

Wenjian Yang ◽

Gianluigi Zaza ◽

Ching-Hon Pui ◽

...

Keyword(s):

Gene Expression ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Leukemia Cells ◽

Cancer Resistance ◽

Childhood All ◽

Pathway Gene ◽

Folate Pathway ◽

B Lineage ◽

Lower Expression

Abstract Methotrexate (MTX) is an essential treatment component for acute lymphoblastic leukemia (ALL). The ability of leukemia cells to accumulate MTX in its polyglutamylated form (MTXPG) is recognized as an important determinant of its antileukemic effect. We measured in vivo MTXPG accumulation in leukemia cells from 101 children with ALL, and established that blasts of B-lineage ALL with either the TEL-AML1 (n=24 patients, median 911, range 338 to 5906 pmol/109 blasts) or E2A-PBX1 gene fusion (n=5, median 553, range 364 to 800 pmol/109 blasts) or T-lineage ALL (n=14, median 572, range 284 to 1468 pmol/109 blasts) accumulate significantly lower MTXPG, compared to those of other B-lineage ALL (BNHD, n=39, median 2210, range 186 to 9722 pmol/109 blasts) or hyperdiploid ALL (BHD, n=19, median 4375, range 377 to 9206 pmol/109 blasts) (E2A-PBX1 versus BHD, p=0.008; E2A-PBX1 vs. BNHD, p=0.010; TEL-AML1 vs. BHD, p<0.001; TEL-AML1 vs. BNHD, p=0.004; T-ALL vs. BHD and BNHD, p<0.001; p-values are from pair-wise comparisons using Wilcoxon rank sum test, adjusted for multiple testing using Holm’s method). To elucidate mechanisms underlying these differences in MTXPG accumulation, we used oligonucleotide microarrays (Affymetrix® HG-U133A) to analyze expression of 32 folate pathway genes (53 probe sets) in diagnostic bone marrow blasts from 197 children with ALL. This revealed ALL subtype-specific patterns of folate metabolism gene expression and identified differences in gene expression that discriminated the MTXPG accumulation phenotype in ALL cells. We found significantly lower expression of the reduced folate carrier (SLC19A1, MTX uptake transporter) in E2A-PBX1 ALL; significantly higher expression of breast cancer resistance protein (ABCG2, MTX efflux transporter) in TEL-AML1 ALL; and lower expression of FPGS (catalyzes formation of MTXPG) in T-ALL; consistent with lower MTXPG accumulation in these ALL subtypes. These findings reveal distinct mechanisms of subtype-specific differences in MTXPG accumulation and point to new strategies to overcome this potential cause of treatment failure in childhood ALL.

Download Full-text