Evaluation by multivariate analysis of the differentiation inhibitory factor nm23 as a prognostic factor in acute myelogenous leukemia and application to other hematologic malignancies

The differentiation inhibitory factor nm23 can inhibit the differentiation of murine and human myeloid leukemia cells. We recently reported that nm23 genes were overexpressed in acute myelogenous leukemia (AML), and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML, es...

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Bibliographic Details
Published in:Blood 1998-03, Vol.91 (6), p.1845-1851
Main Authors: YOKOYAMA, A, OKABE-KADO, J, MOTOYOSHI, K, NAGATA, N, HONMA, Y, WAKIMOTO, N, KOBAYASHI, H, SAKASHITA, A, MASEKI, N, NAKAMAKI, T, HINO, K.-I, TOMOYASU, S, TSURUOKA, N
Format: Article
Language:English
Subjects:
Acute Disease
Adult
Aged
Antigens, CD7 - analysis
Biological and medical sciences
Biomarkers, Tumor - biosynthesis
Biomarkers, Tumor - genetics
Cell Differentiation
Chromosome Aberrations
Drug Resistance, Neoplasm
Female
Gene Expression
Hematologic and hematopoietic diseases
Hematologic Neoplasms - genetics
Hematologic Neoplasms - metabolism
Hematologic Neoplasms - mortality
Humans
L-Lactate Dehydrogenase - blood
Leukemia, Myeloid - genetics
Leukemia, Myeloid - metabolism
Leukemia, Myeloid - mortality
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Leukocyte Count
Male
Medical sciences
Middle Aged
Monomeric GTP-Binding Proteins
Multivariate Analysis
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - metabolism
Myelodysplastic Syndromes - mortality
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
NM23 Nucleoside Diphosphate Kinases
Nucleoside-Diphosphate Kinase
Prognosis
Proportional Hazards Models
Remission Induction
RNA, Messenger - biosynthesis
RNA, Neoplasm - biosynthesis
Survival Analysis
Transcription Factors - biosynthesis
Transcription Factors - genetics
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Summary:The differentiation inhibitory factor nm23 can inhibit the differentiation of murine and human myeloid leukemia cells. We recently reported that nm23 genes were overexpressed in acute myelogenous leukemia (AML), and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML, especially in AML-M5 (acute monocytic leukemia). To evaluate the importance of nm23 expression as a prognostic factor in AML, we compared it with other putative prognostic factors in AML. An analysis of the correlation between nm23 expression and the clinical parameters of 110 patients with AML demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and with reduced overall survival. Multivariate analysis using Cox's proportional hazard model also showed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. Especially in AML-M5, nm23-H1 status was the most important prognostic factor. Furthermore, to determine whether we can apply the results observed in AML to other hematologic malignancies, we investigated the relative levels of nm23-H1 and nm23-H2 transcripts in 149 patients with hematologic neoplasms, including 110 with de novo AML, 9 with de novo acute lymphoblastic leukemia, 14 with myelodysplastic syndrome, 16 with chronic myelogenous leukemia (CML), and 5 normal subjects by the reverse transcriptase-polymerase chain reaction. Expression of nm23-H1 was significantly higher in all the hematologic neoplasms, except CML in chronic phase, than in normal blood cells. nm23 may have a prognostic effect in these hematologic malignancies as well as in AML.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.v91.6.1845