Staging and prognosis

Fig. 7.1 Schematic diagram of the translocation that creates the Philadelphia chromosome

BCR

/

lib I 1a I

rannH

Íe3 e6 e12e13le14l e16 e19 I

m-bcr

p190 p210 p210

Fig. 7.2 Structure of the BCR and ABL genes, showing locations of the breakpoints and various mRNAs created with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), the break occurs within a 5.8-kb area spanning BCR exons 13 and 14, originally referred to as exons b2 and b3, and also known as the major breakpoint cluster region (M-BCR). Depending of the site of the translocation, fusion transcripts with either BCR exon b2 or b3 fused to ABL exon a2 can be formed. Each of these fusion mRNAs is transcribed into a 210-kDa chimeric protein (p210BCR-ABL). In the remaining patients with ALL and rarely in patients with CML, characterized clinically by prominent monocytosis, the breakpoints are further upstream in the region between BCR exons 1 and 2, also known as the minor breakpoint cluster region (m-BCR). The resulting e1a2 mRNA is translated into a 190-kDa protein (p190BCR-ABL). Recently, a third breakpoint cluster region (|-BCR) has been identified downstream of exon 19, giving rise to a 230-kDa fusion protein (p230BCR-ABL) associated with some, but not all, cases of the rare Philadelphia chromosome-positive chronic neutrophilic leukemia.

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