Trisomy 8 in Philadelphia chromosome (Ph1)-negative cells in the course of Ph1-positive chronic myelocytic leukemia.

A female patient with chronic myelocytic leukemia (CML) in chronic phase after busulfan and interferon treatment had four different cell lines in her bone marrow. In addition to cells with a normal karyotype there were cells with the Philadelphia chromosome (Ph1), cells with trisomy 8 and Ph1, and cells with trisomy 8 as the sole anomaly.     

A variant Philadelphia chromosome (Ph1) positive chronic myelocytic leukemia

A rare case of variant Philadelphia (Ph1) chromosome positive [46, XX, t (9; 22) (q34; q11), inv (9) (9q22; 22q13)] chronic myelocytic leukemia (CML) was described. The patient, 73 years old female, was hospitalized to our hospital because of leukocytosis. Hematological findings corresponded to those of CMLs. However, this case lacked hepatosplenomegaly. Southern blot analysis using a 3 breakpoint cluster region (bcr) probe revealed a bcr rearrangement. The patient has been in the chronic phase for sixteen months without treatment. Clinical and chromosomal changes are under observation in order to get accumulate data for a pathophysiological analysis of variant Ph1 positive CMLs.     

Philadelphia chromosome (Ph1)-associated leukemias: A family study

In the present study we describe a family in which a mother and her son developed leukemia in close temporal proximity. The boy presented with a clinical picture consistent with acute lymphoblastic leukemia. His mother developed chronic myelogenous leukemia. Using Giemsa banding we demonstrated that both cases had an associated Philadelphia chromosome. Hematologic, cytogenetic, and HLA haplotyping studies were performed, but did not reveal a genetic basis for the high incidence of leukemia in this family.     

Isochromosome (17q) in Philadelphia chromosome (Ph1)-negative juvenile chronic myelocytic leukemia

A dicentric isochromosome of the long arm of one chromosome #17 was the only abnormality present in a 12-year-old boy with Philadelphia chromosome (Ph¹)-negative juvenile chronic myelocytic leukemia. This association does not seem to have been reported in the literature. It is postulated that the finding of an isochromosome (17q) may also have a negative prognostic value in the Ph¹-negative type of chronic myelogenous leukemia.     

Ph1-negative chronic myelocytic leukemia (CML) with an unusual karyotype

A case of Ph¹-negative chronic myelocytic leukemia is reported. Cytogenetic analysis and the development of colonies in soft agar culture 2 months before the clinical manifestation of the acute phase of the disease clearly indicated the bad prognosis of the patient. An extra #8 chromosome was found in 23% of his cells. Also of note was the presence of an abnormal clone characterized by t(12;13).     

Disposition of hydrochlorothiazide (Hct) during phenytoin (Ph) treatment

Summary Plasma levels and urinary recovery of Hct were determined in seven healthy male volunteers. 75 mg Hct were administered as a tablet in a randomised fashion with or without phenytoin pretreatment (300 mg/d). Bioavailability of Hct showed considerable intra- and interindividual variation (32–87% and 42–77% respectively), but phenytoin did not influence the disposition parameters of the diuretic.     

Presence of the Philadelphia chromosome (Ph1) in pokeweed mitogen stimulated lymphocytes during chronic phase of chronic myelocytic leukemia (CML)

There has been a lack of direct cytogenetic studies on lymphocytes in the chronic phase of chronic myelocytic leukemia (CML). Peripheral blood mononuclear cells from seven patients in the chronic phase and on in the blastic phase of Ph1-positive CML were cultured in the presence of phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Preparations adequate for analysis were obtained from eight PHA and five PWM stimulated cultures. Cytogenetic studies on the PWM stimulated cultured cells revealed, in one patient, the presence of the Philadelphia chromosome (Ph1) in 23/25 metaphases. The PHA stimulated lymphocytes from the same patient were all Ph1 negative. Lymphocytes from PHA and PWM stimulated cultures from the other six patients in the chronic phase and the one patient in blastic crisis were all Ph1 negative. The one positive result suggests that some B lymphocytes contain the Ph1 and that there is a common hematopoietic stem cell for B lymphocytes as well as the myeloid, erythroid, and megakaryocytic series.     

New types of unusual and complex Philadelphia chromosome (Ph1) translocations in chronic myeloid leukemia

Nine cases of Philadelphia chromosome-positive chronic myeloid leukemia with an aberrant translocation are reported. In three cases an unusual translocation was found, the recipient chromosome being Nos. 14, 17, and 18, respectively. In six cases the translocation involved a third chromosome in addition to Nos. 9 and 22: there were two cases involving chromosome No. 1, two involving chromosome No. 14, one involving chromosome No. 3, and one involving chromosome No. 12. The clinical significance of the aberrant translocations and the translocation mechanism is discussed.     

The Philadelphia (Ph) chromosome in leukemia. II. Variant Ph translocations in acute lymphoblastic leukemia

Nearly 20 patients with a masked Philadelphia (Ph) translocation have been described in chronic myelocytic leukemia. We report two instances of acute lymphoblastic leukemia (ALL) with variant Ph translocations. One case, involving a 26-year-old male, was associated with a variant t(14;22)(q32;q11) translocation. The second case involved a 36-year-old male with a more complex translocation, t(9;15;22)(q12;q26;q11). In each case, cells with a masked Ph translocation were observed. These appear to be the first ALL cases reported with a masked Ph chromosome. The findings are discussed in relation to recent knowledge regarding the genesis of the Ph chromosome.     

Philadelphia chromosome (Ph) positive chronic myelocytic leukemia (CML): frequency of additional findings

This article documents the cytogenetic findings in 79 patients with typical Ph-positive chronic myelocytic leukemia (CML). Direct preparations of bone marrow and/or peripheral blood of 46 males and 33 females were studied with different banding techniques. Seventy patients were studied during chronic phase. Three (4.3%) had unusual or complex translocations: t(6;22)(p21;q11), t(8;12;9;22)(p21;q21;q34;q11), and t(9;11;22)(q34;q13;q11). One (1.4%) had a +Ph, 1 (1.4%) had a +8, 1 (1.4%) had a del(3)(p13,p23), and 4 of 30 males (13.3%) showed loss of Y chromosome. Five of 8 cases studied during blast crisis had additional abnormalities. The +8 occurred in 4 cases, +10 and +19 each in 3 cases, +6, + 9q+, and +13 each in 2 cases, and +5, +11, +14, +21, +Ph, i(17q), dic(1;9), and structural abnormalities of chromosomes #1, #5, #12, and #13 each in 1 case. Two cases studied in blast crisis alone had complex translocations leading to the Ph. Because it cannot be ruled out that these translocations are secondary, they were not included in the calculation of the frequency of atypical translocations.     

The Philadelphia (Ph) chromosome in leukemia. III. Complex Ph translocation plus inversion in chronic myelocytic leukemia

Remarkable chromosome abnormalities were observed in bone marrow cells from a woman with chronic myelocytic leukemia and atypical tuberculosis due to Mycobacterium avium-intracellulare infection. Four chromosome breaks occurred at bands 1p13, 1q32, 11p15, and 22q11. These breaks resulted in a complex Philadelphia (Ph) translocation between chromosomes #1, #11, and #22 and in an inversion of chromosome #1. Oncogenes on these chromosomes include N-ras and c-sk on chromosome #1, c-H-ras on chromosome #11, and c-sis on chromosome #22. Complex chromosome rearrangements may facilitate multiple oncogene changes, thereby permitting several steps in cancer development to occur simultaneously.