In:
Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2950-2950
Abstract:
In patients with chronic myeloid leukemia who do not reach a (near) complete cytogenetic response upon treatment, the disease progresses over months to several years from an indolent, chronic phase into a rapidly fatal blast crisis. Events that are responsible for this transformation process are largely unknown. To identify changes occurring in the course of the disease, we performed cDNA subtraction on sequentially stored peripheral blood mononuclear cell pellets, collected from a single CML patient throughout the course of disease. Thirty-three differentially expressed sequences were identified, of which 28 corresponded to known genes. Quantitative PCR confirmed cDNA subtraction results for 24 of 25 tested genes. Differential expression levels ranged from 〈 2- to 106-fold. The sequences that were identified include genes encoding for several apoptosis related proteins, cell cycle proteins, interleukins/chemokines, heat shock proteins and a DNA repair enzyme (see table). Thus far, expression levels of eight genes have been tested in sequential samples of three to six additional CML patients, gathered throughout their disease course. PBCEF, IL8, IL6, CCL4 and YWHAZ show comparable patterns as the index patient; expression levels of APEX, NXF1 and PRG1 were consistent with those of the index patient in only a part of the additional patients. More patients are being tested on these and remaining genes. We conclude that this set of genes can be considered as a valuable starting point for further research on the causes of disease transformation in CML. Name of gene Accession No. Fold difference (Q-PCR) * Genes hypothetically encoding proteins, ** Reverse to subtraction result, ***orf: open reading frame diagnosis 〉 blast crisis: PRG1 NM_002727 14 IVNS1ABP NM_006469 〈 2 MPO NM_000250 ND blast crisis 〉 diagnosis: EMR1 NM_001974 〈 2 CD96 NM_198196 3 GAS2 NM_005256 12 CHI3L2 NM_004000 11 late chronic phase 〉 blast crisis: IL8 NM_000584 2 S100A8 NM_002964 16 FPR1 NM_002029 51 LYZ NM_000239 ND MEN1 AF001893 ** blast crisis 〉 late chronic phase: MMRN NM_007351 6 NACSIN NM_015252 24 LARS NM_020117 7 FLJ25286* NM_152546 ND C5orf13*** NM_004772 ND C15orf15*** NM_016304 ND FLJ10849* NM_018243 ND diagnosis 〉 late chronic phase: DNAJB1 NM_006145 35 HSPA8 NM_006597 5 NXF1 NM_006362 2 DC2 NM_021227 〈 2 APEX1 NM_080648 4 RPS6 NM_001010 〈 2 EEF1A1 NM_001402 3 FLJ25286* NM_152546 ND late chronic phase 〉 diagnosis: SAT NM_002970 7 CCL4 NM_002984 106 YWHAZ NM_145690 3 PBEF1 NM_182790 7 IL6 NM_000600 42 IL8 NM_000584 9
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V104.11.2950.2950
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2004
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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