Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocytic leukemia which was unusual in the sense of the occurrence of a myeloid-lymphoid conversion and lack of an apparent chronic phase. Cases 2 and 3 appeared to be de novo Ph+ ALL.</p

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.</p

Aclarubicin in the treatment of elderly patients with acute nonlymphocytic leukemia.

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.</p

Molecular analysis of chronic myelocytic leukemia and related diseases

Chronic myelocytic leukemia (CML) is cytogentically characterized by the Philadelphia chromosome (Ph(1)) resulting from a reciprocal translocation t(9;22)(q34;q11). The breakpoints on chromosome 22 are clustered within a limted region of 5.8 kilobase (kb), termed the breakpoint cluster region (bcr). Herein the bcr rearrangement was examined to clarify the relationship between CML and related diseases. By Southern blot analysis of DNA, the bcr rearrangements were recopnized (bcr(+)) in 52 of 54 standard Ph(1)-positive (Ph(1+)) CML and all 3 variant Ph(1+)CML［46, XX, t(9;22;13)(q34;q11;q22),46, XX, t89;22)(q21;q11) and 46, XX, t(9;22)(q34;q11),inv (9)(9q22;22q13)］. The site of breakpoint within bcr was not a prognostic factor in Ph(1+)CML. On the other hand bcr rearrangements were negative (bcr(－)) in 2 juvenile CML (JCML), 3 chronic neutrophilic leukemia (CNL), 9 chronic myelomonocytic leukemia (CMML), 8 polycythemia vera (PV), 15 essential thrombocythemia (ET) and 4 myelofibrosis (MF) patients. In 5 patients with Ph(1)-negative (Ph(1－)) CML/unclassifid chronic myeloproliferative disorders (UCMPD), 2 were bcr(+) and 3 were bcr(－), which strongly suggested the existence of Ph(1－)bcr(－)CML