Analysis of molecular breakpoint and m‐RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukaemia: no correlation with clinical features, cytogenetic response, duration of chronic phase, or survival

Abstract

Two hundred and nineteen cases of Ph+ve CML and 15 Ph-ve, BCR+ve CML cases have been analysed to determine the breakpoint site and its relationship to clinical features, cytogenetic response, duration of chronic phase and survival. 119 cases have had RNA analysis performed to determine the type of BCR/ABL transcript and have also been analysed in a similar way. Presenting features at diagnosis including age, sex, white-cell count and platelet count showed no significant difference for those with 5' and 3' breakpoints and those with either b2a2 or b3a2 BCR/ABL transcripts. However, in a subgroup of patients whose presenting white-cell count was < 100 x 10(9)/l, those with b3a2 transcript did have a significantly higher platelet count. Analysis by Sokal risk grouping showed no difference for 5' or 3' breakpoints but a trend for lower stage among those with b2a2 transcripts. No correlation was found either for genomic breakpoint site or BCR/ABL RNA transcript in terms of duration of chronic phase or survival. When stratified by randomized therapy, either interferon-alpha or standard chemotherapy, no difference was noted in relation to genomic breakpoint site or BCR/ABL transcript. Cytogenetic response was not related to the molecular findings.

Collection of Philadelphia-negative peripheral blood progenitor cells in unselected patients with chronic granulocytic leukaemia

“…The position of the breakpoint and RNA transcript, and their association with survival 28 and response to interferon 25,29 have been the subject of considerable debate. To date, a consistent association has not been shown.…”

“…Total registration of all new cases of CGL has been in place since January 1988. A median of 25 new cases present per annum (range [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. 4 From January 1994 a programme of early intervention for patients under 60 years of age was begun with the cooperation of all 25 regional haematologists.…”

True

“…The majority of CML patients have transcripts with the b3-a2 (55%) or b2-a2 (40%) junctions ( Figure 10b). 120,121 In 5% of cases, both b3-a2 and b2-a2 transcripts can be formed as a result of alternative splicing. 112,120,121 So far, no clear difference in clinical outcome has been reported between the two BCR-ABL p210 transcripts.…”

“…120,121 In 5% of cases, both b3-a2 and b2-a2 transcripts can be formed as a result of alternative splicing. 112,120,121 So far, no clear difference in clinical outcome has been reported between the two BCR-ABL p210 transcripts. 112,120 Occasionally in CML patients other breakpoints both in BCR and ABL genes have been described.…”

“…112,120,121 So far, no clear difference in clinical outcome has been reported between the two BCR-ABL p210 transcripts. 112,120 Occasionally in CML patients other breakpoints both in BCR and ABL genes have been described. In very rare cases of Ph + CML (Ͻ10 cases reported), the breakpoint in the BCR gene involves the ALL-associated m-bcr region, which results in the exclusive production of the smaller p190 BCR/ABL fusion protein (see Section 4).…”