Chronic myelogenous leukemia: amplification of a rearranged c-abl oncogene in both chronic phase and blast crisis

The specific genetic events that distinguish the blast crisis from the chronic phase cells of chronic myelogenous leukemia (CML) are unknown. The most common karyotypic change that occurs as CML evolves from chronic phase to blast crisis is the development of multiple Philadelphia (Ph1) chromosomes, each of which is presumably harboring a translocated c-abl oncogene. We describe here a patient with CML who presented in lymphoid blast crisis with three Ph1 chromosomes/metaphase associated with an amplified, rearranged c-abl oncogene fragment and high levels of the aberrant 8-kilobase bcr-abl transcript. This rearranged c-abl fragment was amplified to a similar degree in both the patient's blast crisis cells and in his terminally differentiated granulocytes, but the level of the aberrant CML-specific bcr-abl transcript was some eight- to 16-fold higher in the blast crisis cells v the granulocytes. This analysis indicates that genomic amplification of a translocated c-abl oncogene, although perhaps important in the evolution of CML, nevertheless cannot, by itself, be the sole genetic event giving rise to blast crisis.

Chronic myelogenous leukemia: amplification of a rearranged c-abl oncogene in both chronic phase and blast crisis

The specific genetic events that distinguish the blast crisis from the chronic phase cells of chronic myelogenous leukemia (CML) are unknown. The most common karyotypic change that occurs as CML evolves from chronic phase to blast crisis is the development of multiple Philadelphia (Ph1) chromosomes, each of which is presumably harboring a translocated c-abl oncogene. We describe here a patient with CML who presented in lymphoid blast crisis with three Ph1 chromosomes/metaphase associated with an amplified, rearranged c-abl oncogene fragment and high levels of the aberrant 8-kilobase bcr-abl transcript. This rearranged c-abl fragment was amplified to a similar degree in both the patient's blast crisis cells and in his terminally differentiated granulocytes, but the level of the aberrant CML-specific bcr-abl transcript was some eight- to 16-fold higher in the blast crisis cells v the granulocytes. This analysis indicates that genomic amplification of a translocated c-abl oncogene, although perhaps important in the evolution of CML, nevertheless cannot, by itself, be the sole genetic event giving rise to blast crisis.

Karyotypic Evolution and Long-Term Effective Population Sizes of Birds

Rates of karyotypic change in birds are used to estimate that, over the longterm history of a wide assortment of genera, avian effective population sizes have averaged on the order of 100. This result is consistent with the results of electrophoretic studies of geographic variation of allelic frequencies within species but is somewhat less consistent with the results obtained from demographic modeling. Three methodologically independent analyses have now corroborated the hypothesis that avian effective population sizes are typically of the order of 102 or larger.

Karyotypic conservatism in the genus Lepus (order Lagomorpha)

The G- and C-banded chromosomes of six species of hare (genus Lepus) are presented and compared. No variation in gross chromosome morphology or banding pattern was observed indicating that speciation in this widespread genus has not involved karyotypic change.

Clonal chromosome abnormalities in patients with Waldenstrom's and CLL- associated macroglobulinemia: significance of trisomy 12

We performed cytogenetic analyses by Q- and G-banding techniques of unstimulated or B-mitogen-stimulated spleen, bone marrow, and peripheral blood cells from six patients with malignant macroglobulinemia [two with Waldenstrom's macroglobulinemia (WM) and four with chronic lymphocytic leukemia associated macroglobulinemia (CLL-M)]. Normal karyotypes were obtained in two of the treated patients (one with WM in remission and the other with CLL-M in relapse). An extra chromosome 12 (trisomy 12) was observed in all four untreated patients. In patient no. 2 (K.R.) and no. 3 (F.G.) with CLL- M, an abnormal karyotype, with trisomy 12 as the only abnormality, was identified. In patient no. 1 (C.C.) with WM, there were two clonal chromosome changes, identified: 47, XX, -9, +12, plus marker chromosome and 48, XX, -9, +12, plus both marker and minute chromosomes. In patient no. 4 (R.M.) with CLL-M, a minute chromosome with or without loss of a G-group chromosome was seen in some metaphases without trisomy 12, in addition to metaphases with trisomy 12 alone. Each of the four untreated patients with WM or CLL-M had clonal chromosome abnormalities, suggesting that chromosome changes may be more frequently associated with WM or CLL-M than with typical CLL without macroglobulinemia. These observations also suggest that trisomy 12 may be the primary karyotypic change in malignant macroglobulinemia, whereas the appearance of the minute or marker chromosome as well as the loss of G-group chromosomes or chromosome no. 9 may be secondary karyotypic changes resulting from clonal evolution in these malignancies.

Clonal chromosome abnormalities in patients with Waldenstrom's and CLL- associated macroglobulinemia: significance of trisomy 12

We performed cytogenetic analyses by Q- and G-banding techniques of unstimulated or B-mitogen-stimulated spleen, bone marrow, and peripheral blood cells from six patients with malignant macroglobulinemia [two with Waldenstrom's macroglobulinemia (WM) and four with chronic lymphocytic leukemia associated macroglobulinemia (CLL-M)]. Normal karyotypes were obtained in two of the treated patients (one with WM in remission and the other with CLL-M in relapse). An extra chromosome 12 (trisomy 12) was observed in all four untreated patients. In patient no. 2 (K.R.) and no. 3 (F.G.) with CLL- M, an abnormal karyotype, with trisomy 12 as the only abnormality, was identified. In patient no. 1 (C.C.) with WM, there were two clonal chromosome changes, identified: 47, XX, -9, +12, plus marker chromosome and 48, XX, -9, +12, plus both marker and minute chromosomes. In patient no. 4 (R.M.) with CLL-M, a minute chromosome with or without loss of a G-group chromosome was seen in some metaphases without trisomy 12, in addition to metaphases with trisomy 12 alone. Each of the four untreated patients with WM or CLL-M had clonal chromosome abnormalities, suggesting that chromosome changes may be more frequently associated with WM or CLL-M than with typical CLL without macroglobulinemia. These observations also suggest that trisomy 12 may be the primary karyotypic change in malignant macroglobulinemia, whereas the appearance of the minute or marker chromosome as well as the loss of G-group chromosomes or chromosome no. 9 may be secondary karyotypic changes resulting from clonal evolution in these malignancies.