Peter E. Hollings

Essential thrombocythaemia and the Philadelphia chromosome

Six adult patients presented with clinical features of essential thrombocythaemia. Five of the patients, although Ph‐positive, have maintained these features without evidence of leukaemia; in one case for 9 years. A sixth patient developed leukaemic blast crisis following a persistently high platelet count over 4 years. Her cells were Ph‐negative, but hybridization of gene probes to chromosomes in situ and to leukaemic DNA showed that the abl oncogene had moved to the breakpoint cluster region (bcr) on the normal chromosome 22. This patient has the same molecular gene change as occurs in some cases of Ph‐negative chronic myeloid leukaemia (CML) whose leukaemic cells likewise show no evidence of chromosomal translocation. Molecular studies are essential for the correct diagnosis of these patients. The Ph genomic lesion appears to have a range of leukaemic expression which includes thrombocythaemia as well as chronic myeloid leukaemia and acute lymphatic leukaemia.

An identical t(Y;1)(q12;q21) in two patients with myelodysplastic syndromes

Two male patients with myelodysplastic syndromes, one with refractory anemia with excess blasts (RAEB), the other with chronic myelomonocytic leukemia both had in their bone marrow and peripheral blood cells the same abnormal karyotype 46,X,-Y, + der (Y)t(Y;1)(q12;q21). This abnormality produced trisomy for the 1q21-1qter region of chromosome 1. In addition to the t(Y;1), the patient with RAEB had a del(20)(q11) abnormality in separate CFU-GM and BFUe progenitor cell populations. The t(Y;1) clone of this patient underwent chromosomal evolution with the acquisition of trisomies for chromosomes 2, 6, 8, and 9. Cytogenetic analysis of serial peripheral blood samples showed that the t(Y;1) clone and its derivatives gradually replaced that with the 20q- abnormality. Metaphase cells trisomic for chromosomes 2, 6, 8, and 9 were found predominantly in the CFU-GM population and only rarely in BFUe colonies, suggesting that chromosomal evolution was largely confined to the granulocytic lineage.

Abnormal chromosome 16 in clonogenic eosinophils from a case of acute myeloid leukemia (FAB,M2)

A case of acute myeloid leukemia (AML, FAB M2) is described in which the leukemic karyotype showed several numerical and structural cytogenetic abnormalities including an abnormal chromosome 16 with breakpoint at band q22, monosomy for chromosomes 5 and 7, and a single pair of double minute chromosomes. There was no patient history of treatment for a previous malignancy or occupational exposure to mutagens. Bone marrow eosinophilia was seen at presentation for refractory anemia with excess blasts in transformation and when AML was diagnosed. When bone marrow buffy coat cells were cultured in soft agar in the presence of colony stimulating factor, 19% of the colonies and 20% of the clusters were of eosinophils. Cytogenetic examination of pooled eosinophil colonies showed the marker chromosomes that identified the leukemic population.

Deletion 20q in association with Philadelphia chromosome positive acute lymphoblastic leukemia: A report of two cases

Cytogenetic deletions involving the long arm of chromosome 20 are thought to be characteristic of myeloid disorders. We report clinical and cytogenetic observations of two adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia: one with a smaller 20q deletion that was the sole cytogenetic abnormality in a persisting remission clone, the other with a larger 20q deletion that was a late addition to the leukemic clone at disease relapse following allogeneic bone marrow transplantation.

Growth Characteristics in vitro of Myeloid Leukaemic Cells with t(6;9)

We report an analysis of in vitro growth characteristics of leukaemic cells from five patients with t(6;9)(p23;q34). Consistent with other reports of this abnormality, our patients were comparatively young (median age at diagnosis, 29 years), and responded poorly to conventional treatment (median survival from diagnosis, 10 months). During active disease the CFU-GM growth patterns were characterized by an abundance of granulocytic aggregates (mostly 20-100 cells in size) whose leukaemic origin was confirmed by cytogenetic analysis. During remission induction, colonies derived from regenerating normal progenitor cell colonies could be distinguished from those derived from persisting leukaemic cells on the basis of differences in size, morphology, in situ staining characteristics, and karyotype. Remission growth patterns were those of a normal bone marrow. Our findings add to a growing recognition that the t(6;9) identifies a subset of leukaemic patients with distinctive clinical, haematologic, molecular, and in vitro growth characteristics for whom conventional treatment offers little hope of cure or long survival.

Karyotypic evolution in a B-cell lymphoma.

A B-cell lymphoma in the lung of a 59-year-old woman showed a near-pentaploid karyotype and chromosomal changes indicating a t(8;14) in cells from a pleural aspirate. Cells from metastases to the skin and a second pleural aspirate were pseudodiploid, but showed separate further complex cytogenetic changes. Among these was a 14q+ chromosome, but the #8 chromosomes apparently were normal. It is suggested that there was a loss of the derivative 8q- chromosome from the t(8;14) followed by homozygozity of the normal #8 chromosome.

Identification of three RFLPs at the HCK locus on chromosome 20

New HindIII, RsaI and TaqI restriction fragment length polymorphisms (RFLPs) within the haemopoietic cell kinase gene in chromosome band 20q11.2 are described. These RFLPs provide a useful marker for linkage analysis in proximal 20q.