Chromosomes and causation of human cancer and leukemia.VI. Blastic phase, cellular origin, and the Ph1 in CML

Abstract

The cytogenetic, histologic, and pertinent clinical data on 107 cases of CML from our laboratory and those from the literature on the incidence of Ph1‐negative cells in marrows of patients with Ph1‐positive CML have been collected and summarized. In addition, the distribution of multiple Ph1‐chromosomes in 5 cases of CML, with and without the blastic phase, has been described and discussed. The findings served as a basis for caution in utilizing the high incidence of Ph1‐positive cells in the marrows of the preponderant number of patients with CML as support for the unicellular stem cell origin of such cells. The occurrence of Ph1‐negative cells in significant percentages in some patients with chronic myelocytic leukemia indicates that several other hypotheses, including a multi‐stem cell origin of marrow cells, are compatible with the observations in CML.

Chromosomes and causation of human cancer and leukemia.VIII. DMS chromosomes in a neuroblastoma

“…Chromosome analysis was performed on bone marrow material and tumor tissue directly, without resorting to culture, according to previously discussed techniques.1' Blood culture for chromosome analysis was accomplished as previously described. 16 The DMS were either counted in the microscope or, when they were present in large numbers, from photographs taken of the cells. Karyotypes were prepared from representative cells.…”

“…Except for the Ph1 chromosome in chronic myelocytic leukemia, no consistent or characteristic karyotypic picture or anomaly has emerged for any particular human neoplastic process. 16 Nevertheless, in certain areas, the cytogenetic findings in human cancer and leukemia have been of help in the differential diagnosis of a malignant from a benign condition (eg., cervical cancer vs. dysplasia), in the prediction of leukemic relapse, and in the interpretation of the karyotypic changes as they relate to the causation of human neoplasia.…”

The Significance of Ph1 Mosaicism: a Report of Six Cases of Chronic Granulocytic Leukaemia and Two Cases of Acute Myeloid Leukaemia

“…In CGL the usual picture at presentation is a 100% Ph'-positive bone marrow; less than 10% of Ph*-positive patients showing persistence of karyotypically normal cells in the marrow (Whang-Peng et al, 1968;Sandberg et al, 1971;Sakurai et al, 1976). Exceptionally, the Ph' may be observed early in the course of CGL prior to the onset of clinical symptoms (Canellos & -Peng, 1972).…”

Cytogenetic Studies During Remission of Blastic Crisis in a Patient with Chronic Myelocytic Leukaemia

“…The Philadelphia (Phl) chromosome can be found in 85-90 % of patients with the typical pattern of chronic myelocytic leukaemia (CML) (Ezdinli et al 1970, Fitzgerald et a1 1963, Speed & Lawler 1964, Tough et al 1963. It is the only consistent chromosomal abnormality found in, a neoplastic disease, and except in rare patients with diseases such as acute myelocytic leukaemia (Kiossoglou et al 1965b, Whang-Peng et a1 1970 or myelofibrosis , Sandberg et al 1971 occurs olnly in CML (Speed dk Lawler 1964, Tough et a1 1963, Trujillo & Ohno 1963.…”

“…During blastic crisis further chromosomal aberrations may occur, including duplication of the Phl chromosome and aneuploidy of other chromosomes. Although a number of reports describe the chromosome changes occurring with blastic transformation (Kemp et a1 1962, Kiossoglou et a1 1965a, Krompotic et al 1968, Meisner et al 1970, Sandberg et al 1971 sim from the blastic crisis (Garson et al 1969).…”