The Philadelphia Chromosome Ph

Working in Philadelphia in 1960, Nowell and Hungerford discovered a "minute chromosome," an abnormal G-group chromosome, in bone marrow cells from two patients with CML.2 They were the first to identify a chromosomal abnormality that is consistently associated with a human malignancy. Approximately a decade later it was recognized that the "Philadelphia chromosome" is in fact a shortened chromosome 22 and that it is an acquired lesion of the leukemic clone as nonhematopoietic tissues such as bone marrow fibroblasts have a normal kary-otype in patients with CML.1,6,7 In 1973, Rowley et al.8 found that the abnormality was a reciprocal translocation of segments between chromosomes 9 and 22, hence termed t(9;22). The exact breakpoints of the translocation have been identified as t(9;22)(q34.1;q11.21) using cell synchronization and high-resolution banding techniques (Figure 4-1).9 Work in the 1980s and 1990s unraveled many of the molecular defects underlying the cytogenetic events illuminating the role of specific BCR and ABL sequences and the oncogenic potential of the chimeric BCR-ABL products.10-15

The Ph is the hallmark of CML where it is observed in almost 95 percent of the patients. It is, however, not specific for CML as it occurs in up to 5 percent of children and 15 to 30 percent of adults with ALL and in a small percentage of patients with acute myeloid leukemia (AML) in whom no evidence of a preceding CML phase is found.16 Although the Ph in the acute leukemias is cytogenetically identical to that in CML, the molecular rearrangements are frequently different and the prognosis of Ph-positive acute leukemias is remarkably poor when compared to acute leukemias that do not demonstrate the Ph.

Soon after the identification of t(9;22), complex Ph translocations have been recognized that may involve up to five chro

Figure 4-1. The Philadelphia chromosome is a shortened chromosome 22 that results from a reciprocal translocation between the long arms of chromosomes 9 and 22 (arrows). G banding of metaphase spreads. (Courtesy of Dr. A. Glassman, Cytogenetics Laboratory, The University of Texas M.D.Anderson Cancer Center.)

Figure 4-1. The Philadelphia chromosome is a shortened chromosome 22 that results from a reciprocal translocation between the long arms of chromosomes 9 and 22 (arrows). G banding of metaphase spreads. (Courtesy of Dr. A. Glassman, Cytogenetics Laboratory, The University of Texas M.D.Anderson Cancer Center.)

mosomes, always including 22 and 9.17 Variant translocations demonstrate involvement of chromosome 22 and a chromosome other than 9 or vice versa.18,19

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment