Abstract
The Philadelphia (Ph1) chromosome results in a fusion of portions of the BCR gene from chromosome 22 and the ABL gene from chromosome 9, producing a chimeric BCR-ABL mRNA and protein. In lymphoblastic leukemias, there are two molecular subtypes of the Ph1 chromosome, one with a rearrangement of the breakpoint cluster region (bcr) of the BCR gene, producing the same 8.5-kilobase BCR-ABL fusion mRNA seen in chronic myelogenous leukemia (CML), and the other, without a bcr rearrangement, producing a 7.0-kilobase BCR-ABL fusion mRNA that is seen only in acute lymphoblastic leukemia (ALL). We studied the molecular subtype of the Ph1 chromosome in 11 cases of Ph1-positive ALL, including 2 with a previous diagnosis of CML, using a sensitive method to analyze the mRNA species based on the polymerase chain reaction (PCR). We observed unexpected heterogeneity in BCR-ABL mRNA in this population; in particular, 1 of 6 bcr-rearranged cases and 1 of 5 bcr-unrearranged cases contained none of the known fusion mRNA species, while 1 of the bcr-rearranged cases contained both. This latter case is particularly interesting because it suggests that the acquisition of an additional BCR-ABL fusion species may be a mechanism of disease progression. We ...Continue Reading
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