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9;22;15 complex translocation in Ph1 chromosome positive CML revealed by Giemsa-11 procedure in apparent lymphoid cells of blastic crisis.

A Ph1 chromosome positive chronic myeloid leukemia patient whose chronic phase lasted 7.5 years experienced a blastic transformation originating in the spleen. The spleen was infiltrated with undifferentiated blast cells that on cytogenetic analysis had a hyperdiploid karyotype and were Ph1 chromosome positive. The blast cells were negative for PAS, peroxidase. Sudan black and esterase stains. They were non-T, non-B with TdT activity. Remission was achieved in response to prednisone, vincristine, and adriamycin. Ph1 positive cells were present with cells responding to PHA stimulation throughout the course of the disease. A Giemsa-11 staining procedure male possible the ascertainment of a No. 9 translocation chromosome in blastic crisis cells that had also been present in Ph1 chromosome positive cells early in the disease. The presence of this translocation initially in myeloid cells and subsequently in apparent lymphoid cell types suggests the origin of this patient's leukemia as a pluripotential stem cell.

Azure Stains↗

17p+ in a patient with chronic myelogenous leukemia (CML): its differentiation from an isochromosome 17,[i(17q)].

Bone marrow chromosomes are usually of such poor quality as to make it difficult to band them with QFQ or GTG techniques. Because of the possibility that many nonrandom chromosomal abnormalities are present in hematologic disorders, a more reliable banding technique is necessary. Using the RFA technique an abnormality thought to be isochromosome 17, [i(17q)] in a patient with chronic myelogenous leukemia, was revealed to be 17 p+.

Aged↗

Dicentric isochromosome for the long arm of chromosome #17, dic i(17q), in a patient with chronic myelogenous leukemia (CML).

Cytogenetic studies in a 33-year-old male patient with chronic myelogenous leukemia of 7 years duration revealed a so-called i(17q) chromosome marker and other cytogenetic abnormalities during the early phase of blastic crisis which were not present at diagnosis. Careful morphologic examination of this marker using G- and C-banding techniques revealed it to be a dicentric chromosome with a very short intercentromeric area. The fact that the dicentric nature of this marker was not apparent with the conventional Giemsa stain emphasizes the usefulness of the C-banding technique in defining the origin of this important cytogenetic marker.

Adult↗

Ph1 -positive CML associated with megakaryocytic hyperplasia and thrombocythemia and an abnormality of chromosome no. 3.

A patient with Philadelphia (Ph1) chromosome positive chronic myelocytic leukemia is described, who had in blast crisis in addition an abnormality of chromosome No. 3; ins(3; 3)(q26; q21q26). This abnormality might be connected with hyperplasia of megakaryocytes and thrombocythemia, as recently reported in patients with acute leukemia. In the initial phase of the disease our patient had also thrombocythemia, hyperplasia of megakaryocytes with morphological abnormalities. Furthermore, when blast cells were culture in diffusion chambers, differentiation into several cell lines occurred but not into megakaryopoiesis. It is, therefore, concluded that the involved band on chromosome No. 3 might contain the locus which controls megakaryocytic proliferation and platelet production but additional factors seem to be required for their expression.

Bone Marrow↗

Translocation t(3;20) associated with thrombocythemia in Ph-positive CML.

A patient with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia is described who also developed an abnormality of chromosome #3, i.e., t(3;20)(p21;p13), in blast crisis. This abnormality may be connected with the advent thrombocythemia. The disease was a thrombopenia in the initial phase.

Adult↗

Two apparent Philadelphia chromosomes arising from translocations with different chromosomes in a patient with CML: 46,XY,t(7;22)(p22;q11),t(9;22)(q34;q11).

Chromosome studies on bone marrow cells and unstimulated peripheral lymphocytes from a patient with chronic myelogenous leukemia revealed the presence in all cells of two apparent Philadelphia chromosomes: one resulting from the classical translocation with a chromosome #9, and the other arising from a translocation between chromosomes #22 and #7. There was no normal chromosome #22. Some of the cells also had an i(17q), indicative of blast crisis. Repeated chromosome studies at different times during the course of the disease revealed the evolution of additional karyotypic changes. All cells from later samples had an extra #8; some of these cells had a third Philadelphia chromosome, whereas, others had a second Y chromosome. Although a few normal cells were seen in PHA-stimulated lymphocyte cultures, indicating that the patient has a normal constitutional karyotype, most of the cells had a karyotype identical to that found in unstimulated cultures. This unusual karyotype, 46,XY,t(7;22)(p22;q11),t(9;22)(q34;q11), represents the first case in which two apparent Philadelphia chromosomes are present in the leukemic cells from a patient in the absence of a normal #22 chromosome.

Chromosome Banding↗

Duplication of Ph and of 9q+ chromosomes during the blastic transformation of a CML case.

We describe the blastic transformation of a case of chronic myelocytic leukemia in which, among other abnormalities, one extra Philadelphia and one extra 9q+ were observed. Molecular studies and analysis of the clonal evolution of the karyotype led to the interpretation of such an unusual finding as the result of nondisjunction, rather than of a double t(9;22) translocation.

Adult↗

Karyotype evolution in CML: high frequency of translocations other than the Ph.

The karyotypes of 33 Philadelphia-positive chronic myelogenous leukemia patients during the blastic phase are reported. Only three patients (9%) had a Philadelphia clone without further chromosomal aberrations, whereas, all the others had karyotype evolution. Aside from some nonrandom abnormalities (+8, i(17q), +Ph, +19) we found a higher frequency of clones with random structural rearrangements (13 cases, 39.4%) than previously reported. From a clinical point of view, however, the additional chromosomal (structural) abnormalities do not significantly influence the patients' survival.

Adolescent↗

Heteromorphism of C-band positive chromosomal regions in CML patients.

The heteromorphism of constitutive heterochromatin in chromosomes #1, #9, and #16 was investigated in 44 chronic myelocytic leukemia patients and 44 controls using bone marrow and peripheral blood lymphocyte cultures. A significant increase in the length of C-band region in all the three chromosome pairs as well as a statistically significant difference in the homologs of chromosome #1 was observed in chronic myelocytic leukemia patients when compared with the controls. The frequency of inversions was also greater in the patients than in the controls. A random translocation of 22q was found on either homolog of chromosome #9.

Chromosome Banding↗

The application of fluorescent in situ hybridization to detect Mbcr/abl fusion in variant Ph chromosomes in CML and ALL.

We investigated the usefulness of fluorescent in situ hybridization with different-colored major breakpoint cluster region (Mbcr) and Abelson oncogene (abl) probes in clinical practice. In standard Ph chromosomes with a Mbcr breakpoint, these probes produced a fusion of Mbcr and abl signals that was visible in interphase and metaphase cells. The normal range for apparent Mbcr/abl fusion signals in interphase nuclei was established in bone marrow from 25 normal controls. We tested the probes on 35 bone marrow specimens from five normal subjects and 29 patients with various kinds of Ph chromosomes and chronic myelogenous leukemia or acute lymphocytic leukemia. This method produced Mbcr/abl fusion signals in patients with a standard Ph chromosome, simple or complex variants of Ph chromosomes, and "Ph-negative chronic myelogenous leukemia." In metaphase cells of patients with acute lymphocytic leukemia, this method established Ph chromosomes with minor bcr (mbcr) breakpoints. Fluorescent in situ hybridization is a relatively inexpensive and rapid method. When this method is used in conjunction with conventional chromosome analysis, the cytogeneticist can combine the power of complete karyotype studies and the resolution of molecular techniques for patients suspected of having a Ph chromosome.

Bone Marrow Cells↗