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Granulocyte colony-stimulating factor receptor expression and 11q23/MLL genotype in childhood acute lymphoblastic leukemia developing during the first 18 months of life

Leukemia volume 14, pages 337–338 (2000)Cite this article

Granulocyte colony-stimulating factor (G-CSF) regulates myeloid differentiation and is particularly important for neutrophilic granulocyte maturation. Clinically, G-CSF is frequently used to shorten the neutropenic period following intensive multiagent cancer chemotherapeutic regimens.1 Since leukemia cells may express functional G-CSF receptors, it is of importance to assess whether clinical application of G-CSF may have an impact on the course of disease in such cases. Recently, Inukai et al2 described a case of a 20-month-old boy with an acute lymphoblastic leukemia (ALL) bearing an 11q23 translocation and expressing the G-CSF receptor. Of interest, the investigators described that proliferation of leukemia cells was triggered by application of recombinant G-CSF. Furthermore, when eight additional cell lines (1 monocytic, 4 biphenotypic, and 3 lymphoid) with 11q23 translocations (4 t(4;11) and 4 t(11;19)) were analyzed, the investigators detected G-CSF receptor expression in all of them and suggested a possible role of G-CSF in the growth regulation of leukemic cells with 11q23 translocations.2 To address the question of such a genotype–phenotype association in our patient population, we analyzed G-CSF receptor expression and 11q23/MLL genotype in eight ALL patients up to 18 month of age. Patients were selected from the ALL-BFM 90 and ALL-BFM 95 trials of childhood ALL,3 conducted by the Berlin–Frankfurt–Münster (BFM) study group, according to age at diagnosis (⩽18 month) and based on the availability of a cryopreserved initial bone marrow sample. The percentage of leukemic blasts in the selected initial bone marrow samples ranged from 85 to 98%. Immunophenotyping and definition of phenotypic subgroups were essentially as described before.4 Surface antigens were considered positive when ⩾20% of leukemia cells expressed the respective surface marker with more than 98% fluorescence intensity. Myeloid antigens tested for co-expression included CD13, CD33, and CD65s. All these analyses were carried out at the time of diagnosis. Flow cytometric analysis of G-CSF receptor expression was performed by use of cryopreserved initial mononuclear bone marrow samples and the mouse monoclonal anti-G-CSF receptor antibody Mab 129 (IgG1).5 Cytogenetic analyses were carried out at the time of diagnosis using standard techniques.6 MLL genotyping was performed as described before using genomic DNA isolated from cryopreserved initial leukemic bone marrow samples.7

Patient characteristics and results are summarized in Table 1. In flow cytometric analyses, we detected G-CSF receptor expression in two of our eight ALL patients (patient Nos 6 and 7). Both patients were of common ALL phenotype, presented with initial WBCs of less than 50 000/μl, coexpressed a myeloid antigen (CD33), and responded well to induction therapy. They were treated within the intermediate risk group of the ALL-BFM 90 study and are currently in continuous complete remission for more than 4 years. Patient No. 6 had a normal karyotype and a germline MLL configuration. For patient No. 7, no cytogenetic data were available, but in Southern blot analysis a germline MLL configuration was detected as well. An 11q23/MLL rearrangement was observed in patient Nos 1, 2, 4 and 5 (see Table 1). In none of these patients’ leukemia cells did we observe any G-CSF receptor expression. Thus, in contrast to the results of Inukai et al,2 G-CSF-receptor expression and 11q23/MLL rearrangements were not inextricably linked in our patient population.

Table 1  General characteristics, G-CSF receptor expression, and 11q23/MLL genotype in eight childhood acute lymphoblastic leukemia patients
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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover,

    M Stanulla, B Kasper, M Schrappe & K Welte

  2. Oncogenetic Laboratory, University Children's Hospital, Gieβen

    S Viehmann & J Harbott

  3. Department of Hematology, Oncology, and Tumor Immunology, Charité, Humboldt University, Berlin, Germany

    W-D Ludwig

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  1. M Stanulla
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  7. K Welte
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Stanulla, M., Kasper, B., Schrappe, M. et al. Granulocyte colony-stimulating factor receptor expression and 11q23/MLL genotype in childhood acute lymphoblastic leukemia developing during the first 18 months of life. Leukemia 14, 337–338 (2000). https://doi.org/10.1038/sj.leu.2401653

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