Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The selection of optimal treatment among the alternatives that are available is especially difficult in blastic phase of chronic myeloid leukemia (blCML) because of the absence of universally agreed upon criteria for the diagnosis of this phase and the absence of definitions of response. Variable response rates, from less than 10 to greater than 90% have been reported, but the highest response rates, in general, have not been reproducible. The application of strict morphologic, cytogenetic, and molecular biologic studies should provide the means for selection of optimal treatment among the new therapies that will be introduced in the future.
Leukemia 1990 Nov
PMID:Blastic phase of chronic myeloid leukemia (blCML): a proposal for standardization of diagnostic and response criteria. 223 87

We previously administered ara-C at a dose rate of 250 mg/m2/hr for 36-72 hr to patients with leukemia. Gastrointestinal toxicity was dose-limiting. This regimen was modified to an every other day schedule, administering 24-hr periods of high dose continuous infusion ara-C, each followed by a 24-hr rest period. Sixteen patients with relapsed/refractory acute myeloid leukemia (AML) (N = 4), secondary AML (N = 2), relapsed/refractory acute lymphoblastic leukemia (N = 7), or CML in blast crisis (N = 3) received this regimen of three 24-hr infusions with two intercurrent 24-hr rest periods. Grade 3 gastrointestinal toxicity was encountered in 57% of the courses, and hypoplasia was achieved in all patients. Three of the patients died while hypoplastic, two with septicemia and another with intracranial hemorrhage. There were five responding patients (2 CRs, 3 PRs). Median steady-state plasma ara-C levels were 24 microM, 22 microM, and 20 microM during the first, second, and third 24-hr infusions, respectively. Ara-C levels ranged from 4-118 microM during the infusions and were always below 4.5 microM during the rest periods. A significant level of ara-C incorporation into DNA was detected in each of the five patients studied, thus demonstrating that (ara-C)DNA formation is detectable in blasts from patients receiving high dose continuous infusion ara-C therapy. These findings suggest that alternate day continuous infusion ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
Leukemia 1990 Dec
PMID:A phase I study of intermittent continuous infusion high dose cytosine arabinoside for acute leukemia. 224 7

We used a modification of the polymerase chain reaction (PCR) to amplify the specific bcr-abl mRNA from 14 patients with chronic myeloid leukemia (CML) who had previously received non T cell depleted allogenic bone marrow transplantation (BMT). Two types of reactions were used: a single step amplification with 5' and 3' primers, and a double step PCR in which products of the first amplification were reamplified using nested primers. The latter procedure was highly sensitive and capable of detecting one abnormal cell in 10(7) cells. At the time of PCR analysis, all 14 patients were in hematological remission, and 13 were in cytogenetic remission. PCR analysis revealed rearranged bcr-abl mRNA in five patients. The interval from transplant in those five patients ranged from 3 to 63 months. Two of the five positive patients were reexamined after 3 months and were found negative by double step PCR. Our findings suggest that after non-T cell depleted BMT the eradication of the leukemic clone probably occurs in some patients. Other patients, however, proved to have a small number of abnormal cells even at long intervals after BMT, although these cells could only be detected transiently in some patients. The significance of these abnormal cells with respect to the risk of leukemic relapse remains to be determined.
Leukemia 1990 Jan
PMID:Detection of minimal residual disease in chronic myeloid leukemia patients after bone marrow transplantation by polymerase chain reaction. 229

Chronic myelogenous leukemia (CML) is characterized by two distinct phases--chronic and acute. Features of the chronic phase include proliferation and accumulation of mature myeloid cells and their progenitors; differentiation is seemingly intact. In contrast, the acute phase is characterized by impaired differentiation. Acute phase is heterogeneous--granulocytes, lymphocytes, megakaryocytes, and erythroid cells are involved singly or in combination. The t(9;22) translocation, which results in the Ph1 chromosome, is the hallmark of chronic phase CML. Transition to acute phase is often accompanied by additional chromosome abnormalities. Here we suggest that these additional abnormalities determine the phenotype of acute phase CML.
Leukemia 1990 Jan
PMID:Do chromosome abnormalities determine the type of acute leukemia that develops in CML? 229 2

Diaziquone (AZQ) and etoposide (VP-16) were administered as simultaneous 5-day continuous infusions to 27 patients with acute leukemia (22 with acute myeloid leukemia (AML), three with chronic myeloid leukemia in blast crisis (CML-B), and two with acute lymphocytic leukemia) at four different doses in a phase I trial. Gastrointestinal toxicity, primarily stomatitis, was dose limiting, occurring in six of 10 patients at the highest dose level. Diarrhea was the only other grade 3 toxicity noted (three of 10 at the highest dose level). The duration of bone marrow aplasia was excessive at the highest dose (median 48 days to granulocytes greater than 500/mm3, range 33-67) but acceptable (31 days) at the maximum tolerated dose: AZQ 28 mg/m2/day x 5 days, VP-16 150 mg/m2/day x 5 days. Complete remissions were seen in seven patients (six AML, one CML-B) and a partial remission in one patient with AML. The median duration of unmaintained complete remission was 3 months (range 1.5-26+).
Leukemia 1990 Mar
PMID:Continuous infusion diaziquone and etoposide: a phase I study in adult patients with acute leukemia. 231 18

Chronic myeloid leukemia (CML) was diagnosed in a 19-year-old man in 1961, and the disease remained in chronic phase, with occasional exacerbations, for 27 years. In 1976, when the first cytogenetic analysis was performed, t(9;22)(q34;q11) was found as the sole abnormality in all mitoses. During accelerated phase in 1988, a second cytogenetic investigation showed the karyotype 45,XY,t(9;22)(q34;q11),-15,-17,+der(15) t(15;17)(p13;q11). Molecular analysis revealed a rearrangement in the 5' end of the major breakpoint cluster region (M-bcr). With the case presented here, sublocalization of the bcr breakpoint has now been undertaken in altogether five CML patients with extremely long survival. It is noteworthy that in all these cases the chromosome 22 breakpoint was located in the 5' region of the M-bcr.
Leukemia 1990 Jun
PMID:Remarkably long survival of a patient with Ph1-positive chronic myeloid leukemia and 5' bcr rearrangement. 235 44

A patient who was diagnosed with chronic myeloid leukemia remained in chronic phase for 14 years before progressing into a lymphoid blast crisis in 1983. The acute phase was successfully treated, and the patient has remained in an indolent chronic phase to date. Cytogenetic and molecular analysis during this second chronic phase confirm the presence of the Philadelphia chromosome and its transcribed BCR-ABL mRNA. The breakpoint within M-bcr occurred in the 3' portion of the region and expressed a hybrid joining the b3 exon of BCR to the a2 exon of ABL.
Leukemia 1990 Jun
PMID:Molecular analysis of a CML patient with a long duration of chronic phase before and after lymphoid blast crisis. 235 47

Although clinical data support the concept of a graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT), there are few data to support a similar GVL activity following syngeneic BMT in man. To identify cells with a potential antileukemic activity post-BMT, we monitored the immunological reconstitution in a patient with chronic phase chronic myeloid leukemia (CML) who received a syngeneic BMT from his identical twin brother. Peripheral blood mononuclear cells (PBMC) from the donor prior to the transplant and from the recipient posttransplant were cultured with recombinant interleukin-2 to generate lymphokine activated killer (LAK) cells. LAK cells from both sources lysed the cell line target cells K562 and LCL and also recipient and allogeneic CML target cells in a 51Cr release cytotoxicity assay. Donor-derived LAK cells did not kill normal donor marrow. LAK cells had similar effects on granulocyte-macrophage progenitor cells (CFU-GM): LAK cells from both donor pre-BMT and recipient post-BMT inhibited the proliferation of CFU-GM from the patient's CML cells, but again donor LAK cells did not inhibit the colony growth of normal donor marrow. These results suggest that a syngeneic GVL effect is inducible following BMT in man and that this activity may be truly antileukemic and spare normal marrow progenitors.
Leukemia 1990 Apr
PMID:Induction of a syngeneic graft-versus-leukemia effect following bone marrow transplantation for chronic myeloid leukemia. 236 84

The Philadelphia (Ph1) chromosome (22q-), found in more than 90% of patients with chronic myeloid leukemia (CML), is one part of a reciprocal translocation, t(9;22) (q34;q11), in which the oncogene c-abl moves from 9q34 to 22q11. The translocation results in the translation of an aberrant abl-related protein with tyrosine kinase activity. Genetically active genes are known to have chromatin which is hypersensitive to deoxyribonuclease I (DNase I) and to be hypomethylated. Using an in situ nick translation technique on metaphase chromosomes, we have examined DNase I sensitivity and methylation status at the breakpoints 9q34 and 22q11 in bone marrow cells from controls (two cases) and CML patients (three cases). In CML cells DNase I sensitivity was significantly increased, at both breakpoints, in the translocated chromosomes compared with their normal homologues in CML cells and with both homologues in control marrows. A hypermethylated site, seen at 22q11 in normal 22s was hypomethylated on 22q-. The 9q34 region was hypomethylated in normal and translocated chromosomes. DNase I sensitivity, seen at 22q13 in CML cells, was lost following translocation in one of three cases. This technique demonstrates alterations in chromatin conformation and methylation status at translocation breakpoints which may be related to acquired genetic activity at one or both of these sites.
Leukemia 1990 May
PMID:Possible evidence for acquired genetic activity at both chromosomal breakpoints of the Philadelphia translocation in chronic myeloid leukemia. 238 79

It has been suggested that abnormalities of chromosome 3 at bands q21 and q26 are associated with the presence of increased numbers of abnormal megakaryocytes in patients with hematologic malignancies. The pretreatment bone marrows of 287 patients with leukemia (acute myeloid leukemia (AML), 225 patients; acute lymphocytic leukemia (ALL), 36 patients; or chronic myelogenous leukemia in blast crisis (CML-B), 26 patients) were reviewed to identify those with normal or increased numbers of megakaryocytes. Thirty-two patients with AML, one with ALL, and 10 with CML-B had normal or increased numbers of megakaryocytes. Of the 32 patients with AML, 19 patients had significant numbers of mononuclear or binuclear small megakaryocytes as well as megakaryocytes with separated nuclei ("micromegakaryocytes"). Cytogenetic analyses were obtained in 29 of 32 patients with AML and showed inv(3)(q21q26) (one patient); Ph1 (two patients); -5 and/or -7 (seven patients); normal karyotypes (10 patients). No patient with micromegakaryocytes had a chromosomal abnormality associated with a favorable prognosis. Overall, among 225 patients with AML, four had inv(3)(q21q26) or t(3;3)(q21;q26). Only one of these four patients had normal or increased numbers of megakaryocytes, although all four had micromegakaryocytes. One patient with CML-B had inv(3)(q21q26) but had decreased numbers of megakaryocytes and a platelet count of 24 x 10(3)/microliters. All five patients with abnormal chromosome 3 at bands q21 and q26 had additional cytogenetic abnormalities (Ph1 in two patients; -7 in three patients). Mean and median platelet counts were greater than 100,000/microliters for patients with marrow megakaryocytosis regardless of morphology, as well as for the patients with abnormalities involving 3q21 and 3q26. Abnormalities of megakaryocyte morphology, increases in the numbers of megakaryocytes, and normal to increased platelet counts are not uncommon in patients with acute leukemia and CML-B, and are not uniquely associated with changes involving chromosome 3.
Leukemia 1990 May
PMID:Clinical and cytogenetic correlations of abnormal megakaryocytopoiesis in patients with acute leukemia and chronic myelogenous leukemia in blast crisis. 238 80


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