Abstract |
Severe congenital neutropenia (CN) is characterized by a maturation arrest of myelopoiesis at the promyelocyte stage. Treatment with pharmacological doses of recombinant human granulocyte colony-stimulating factor (rh- G-CSF) stimulates neutrophil production and decreases the risk of major infectious complications. However, approximately 15% of CN patients develop myeloid malignancies that have been associated with somatic mutations in the G-CSF receptor (G-CSFR) and RAS genes as well as with acquired monosomy 7. We report a CN patient with chronic myelomonocytic leukemia (CMML) who never received rh- G-CSF. Molecular analysis demonstrated a somatic G-CSFR mutation (C2390T), which led to expression of a truncated G-CSFR protein in the CMML. Normal G-CSFR expression was unexpectedly absent in primary and cultured CMML. In addition, CMML cells showed monosomy 7 and an oncogenic NRAS mutation. In vitro culture revealed a G-CSF-dependent proliferation of CMML cells, which subsequently differentiated along the monocytic/macrophage lineage. Our results provide direct evidence for the in vivo expression of a truncated G-CSFR in leukemic cells, which emerged in the absence of rh- G-CSF treatment and transduces proliferative signals.
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Authors | M Germeshausen, H Schulze, C Kratz, L Wilkens, R Repp, K Shannon, K Welte, M Ballmaier |
Journal | Leukemia
(Leukemia)
Vol. 19
Issue 4
Pg. 611-7
(Apr 2005)
ISSN: 0887-6924 [Print] England |
PMID | 15729385
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- RNA, Messenger
- Receptors, Granulocyte Colony-Stimulating Factor
- Granulocyte Colony-Stimulating Factor
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Topics |
- Adolescent
- Cell Division
- Genes, ras
(genetics)
- Granulocyte Colony-Stimulating Factor
(pharmacology)
- Humans
- In Vitro Techniques
- Leukemia, Myelomonocytic, Chronic
(genetics, pathology)
- Male
- Neutropenia
(congenital, genetics, pathology)
- RNA, Messenger
(metabolism)
- Receptors, Granulocyte Colony-Stimulating Factor
(genetics)
- Tumor Cells, Cultured
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