The suppressor of cytokine signaling-1 is constitutively expressed in chronic myeloid leukemia and correlates with poor cytogenetic response to interferon-alpha.
OBJECTIVE
Interferon-alpha (IFN-alpha) has proven useful for treating chronic myeloid leukemia (CML). However, only 7% of patients achieve a complete cytogenetic response. Although efforts to understand the molecular basis of this resistance to IFN-alpha have been made, the mechanism is still unknown. Because suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling, it has been hypothesized that aberrant SOCS expression could confer resistance against cytokine therapy.


METHODS
In order to analyze the role of SOCS-1 in the acquisition of IFN-alpha resistance in this setting, we examined SOCS-1 mRNA expression using reverse transcription polymerase chain reaction (RT-PCR) in 75 newly diagnosed chronic phase-CML patients who received IFN-alpha therapy.


RESULTS
SOCS-1 was constitutively expressed in 49 (65%) of 75 CML patients at diagnosis. Constitutive SOCS-1 expression was more frequently observed among Hasford high-risk patients (p = 0.05) and was also independently associated with a shorter median progression-free survival time (p = 0.001) and poor cytogenetic response to IFN-alpha treatment (p 0.0001).


CONCLUSIONS
Our data indicate that constitutive expression of SOCS-1 occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease.
Roman-Gomez
José
J
Hematology Department, Reina Sofia Hospital, Cordoba, Spain. peperosa@teleline.es
Jimenez-Velasco
Antonio
A
Castillejo
Juan A
JA
Cervantes
Francisco
F
Barrios
Manuel
M
Colomer
Dolors
D
Heiniger
Anabel
A
Torres
Antonio
A
D000328:Adult; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism* / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D011379:Prognosis; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015996:Survival Rate; D016896:Treatment Outcome
D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins