Philadelphia chromosome positive myelodysplastic syndrome and acute myeloid leukemia—retrospective study and review of literature
Introduction
The Philadelphia chromosome (Ph) was first described as a minute chromosome in patients with granulocytic leukemia by Nowell and Hungerford [1] as a result of partial deletion of the long arm of a G-group autosome. Caspersson et al. further determined that the abnormality involved chromosome 22 [2]. With chromosome banding techniques, Rowley first reported that Ph was a result of reciprocal translocation involving the long arms of chromosomes 9 and 22 [3]. This translocation results in the formation of a hybrid BCR/ABL gene which encodes an enhanced tyrosine kinase activity [4]. It is now known that Ph is found in over 95% cases of chronic myeloid leukemia (CML). Most of the remaining 5% of cases have molecular evidence of a BCR/ABL gene rearrangement even though Ph is not detectable by conventional karyotyping. Cases of CML truly negative for both Ph and a BCR/ABL gene rearrangement are rare [5].
Ph has also been reported in de novo acute leukemia without preceding CML in both the pre-banding and post-banding eras [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. The incidence of Ph+ acute lymphoblastic leukemia (ALL) is estimated to be 17–25% [18], [19], [20], [21] and the percentage of Ph+ acute myeloid leukemia (AML) cases ranges from 0.9 to 3% [18], [20], [21], [22], [23], [24].
We conducted a retrospective study to define the significance of Ph in myelodysplastic syndrome and acute leukemia in the adult patients at this institution and the literature was reviewed.
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Patients and methods
Consecutive cases of leukemia with Ph, t(9;22)(q34;q11), were identified from the Wake Forest University Baptist Medical Center Cytogenetic Laboratory database for the period September 1993 through August 2001. The medical records were also reviewed. This study was approved by the Institutional Review Board at the Wake Forest University School of Medicine.
A literature review was conducted via MEDLINE by searching with “chromosomes, human, pair 9”, “chromosomes, human, pair 22” as medical
Results
One hundred forty-eight cases of t(9;22)(q34;q11) were identified in this time period. The presentation of 124 cases (84%) was that of typical CML in chronic phase. Nineteen cases (13%) presented as de novo ALL without a preceding diagnosis of CML. Two cases (1%) presented as de novo AML and three cases (2%) presented as myelodysplastic syndrome (MDS). During the same time period, our Cancer Registry recorded 89 and 545 cases of ALL and AML, respectively, resulting in estimated incidences of
Discussion
Whether these Ph+ acute leukemias are distinct diseases or merely blastic phases of undiagnosed CML is controversial [19], [27]. Among the cases of Ph+ ALL, approximately 50% have a M-BCR gene rearrangement leading to a p210 kd hybrid protein identical to that of CML, and the other half have a m-BCR gene rearrangement resulting in p190 kd hybrid protein [4], [20]. Most experts contend that Ph+ ALL is a separate entity distinct from blastic phases of CML.
Since Ph+ AML are rare diseases, whether
Acknowledgements
Contribution. Y.-K. Keung contributed to the concept and design, interpreted and analyzed the data, provided drafting of the article, provided critical revisions and important intellectual content gave final approval, provided study materials/patients, collected and assembled the data. M. Beaty interpreted and analyzed the data, provided drafting of the article, provided critical revisions and important intellectual content, gave final approval, and provided study materials/patients. B.L.
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