CONSTITUTIVE EXPRESSION OF GATA-1, EPOR, ALPHA-GLOBIN, AND GAMMA-GLOBIN GENES IN MYELOID CLONOGENIC CELLS FROM JUVENILE CHRONIC MYELOCYTIC-LEUKEMIA

Juvenile chronic myelocytic leukemia (JCML) is a rare disorder of earl y childhood. Characteristic of JCML are the progressive appearance of high levels of fetal hemoglobin (HbF), reflecting a true reversion to a fetal type of erythropoiesis, End the presence of colony-forming cel ls able to grow in vitro spontaneously in the absence of growth factor s. To better understand the relationship between the erythroid abnorma lities and the leukemic process, we analyzed the expression pattern of specific genes related to erythroid differentiation-GATA-1, EPOR, alp ha-globin, beta-globin, and gamma-globin genes-in JCML peripheral bloo d (PB) cells and in vitro-derived colonies. Northern blot analysis of PR cells from five JCML patients indicated levels of GATA-1 transcript s much higher than those usually found in other types of leukemic cell s, and S1 nuclease protection assay detected significantly increased e xpression of gamma-globin mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of single granulocyte-macrophage colony-fo rming unit (CFU-GM) colonies, obtained in vitro in the absence of adde d growth factors from four JCML patients, detected GATA-1, EPOR, and g lobin (alpha and gamma) transcripts in most of the colonies tested, in contrast with control CFU-GM from normal bone marrow, which were posi tive only for GATA-1. Single JCML colonies were tested for the presenc e of two different transcripts; whereas alpha- and gamma-globin genes appeared mostly coexpressed, beta-globin mRNA was detected only in a m inority of the gamma-globin-positive colonies, indicating that the leu kemic pattern of hemoglobin synthesis is mainly fetal. In addition, th e leukemic cells occurring during blast crisis of one of our patients displayed the typical features of a stem cell leukemia (CD34+, CD19-, CD2-, myeloperoxidase-). In this sorted CD34+ population, we detected the presence of a marker chromosome, der(12)t(3;12), previously identi fied in bone marrow cells at diagnosis and an expression pattern super imposable to that of the JCML colonies, consistently displaying a high gamma-globin:beta-globin mRNA ratio. The expression of erythroid mark ers within populations of leukemic cells, both in vivo and in vitro, s upports the hypothesis that abnormal JCML erythroid cells may originat e from the same mutated progenitor that sustains the growth of the leu kemic cells. (C) 1995 by The American Society of Hematology.