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Leukemia‐induced bone marrow depression: Effects of gangliosides on erythroid cell production
Author(s) -
Sietsma Hannie,
Kamps Willem A.,
Dontje Bert,
Hendriks Dick,
Kok Jan W.,
Vellenga Edo,
Nijhof Willem
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990702)82:1<92::aid-ijc16>3.0.co;2-j
Subject(s) - erythropoiesis , erythropoietin , haematopoiesis , bone marrow , biology , cd34 , immunology , cancer research , stem cell , in vitro , cell culture , stem cell factor , ineffective erythropoiesis , ganglioside , endocrinology , medicine , anemia , microbiology and biotechnology , biochemistry , genetics
Bone marrow depression is a common feature in hematological malignancies or other bone marrow‐involving cancers. The mechanism of this hemopoietic suppression resulting in pancytopenia and especially anemia has not been elucidated. Gangliosides can be shed by cancer cells. Therefore, we investigated the effects of exogenously added gangliosides on erythropoiesis in a human and murine in vitro system. A dose‐dependent inhibition of murine colony‐forming‐unit‐erythroid (CFU‐E) and burst‐forming‐unit‐erythroid (BFU‐E) colony growth was observed. Furthermore the maturation of BFU‐Es into CFU‐Es was inhibited. The inhibition by gangliosides was not abolished by increasing the dose of erythropoietin (10 U/ml). FACS‐analysis studies with human CD34 + cells cultured with gangliosides (GM3) , erythropoietin (EPO) and stem cell factor (SCF) demonstrated a strong inhibition on cell growth. This resulted in a significantly higher percentage of immature cells (CD34 + /GpA − , 24% vs. 3%), and a lower percentage of mature erythroid cells (CD34 − /GpA + , 36% vs. 89%). Under these circumstances the effects on erythroid cell growth were much higher than on other cell lineages. The inhibitory effect of gangliosides isolated from acute lymphoblastic leukemic patients on in vitro erythropoiesis suggests that in vivo hemopoietic suppression might have its origin in the gangliosides present and probably shed by the malignant cells in the microenvironment and plasma. Our results show that gangliosides inhibit erythropoiesis in vitro at several stages of development, by a mechanism involving modulation of the maturation of erythroid cells. Int. J. Cancer 82:92–97, 1999. © 1999 Wiley‐Liss, Inc.