scholarly journals Similarities of the Erythrocytes in Juvenile Chronic Myelogenous Leukemia to Fetal Erythrocytes

Blood ◽  
1972 ◽  
Vol 39 (6) ◽  
pp. 778-784 ◽  
Author(s):  
Helen S. Maurer ◽  
Loyda N. Vida ◽  
George R. Honig
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Newborn Infants ◽  
Fetal Hemoglobin ◽  
Hemoglobin Concentration ◽  
Myelogenous Leukemia ◽  
Oxygen Dissociation ◽  
Leukocyte Alkaline Phosphatase ◽  
Characteristic Features ◽  
Erythrocytes Of Newborn Infants

Abstract A 4-yr-old boy was studied who showed typical findings of juvenile chronic myelogenous leukemia, including massive hepatosplenomegaly, thrombocytopenia, low leukocyte alkaline phosphatase, and absence of a Philadelphia chromosome. The erythrocytes of the patient exhibited many characteristic features of erythrocytes of newborn infants: the fetal hemoglobin concentration was greatly elevated (72%); the oxygen dissociation curve of the whole blood was displaced to the left of the curve from normal adult blood; the hemoglobin A2 level and the erythrocyte I antigen titer were reduced; and a structural analysis of the γ-chain of the fetal hemoglobin showed the glycine to alanine ratio in γ-136 to be typical of the neonatal pattern. These findings support the suggestion that juvenile chronic myelogenous leukemia is accompanied by reversion to a fetal pattern of erythropoiesis.

Chronic Myelogenous Leukemia in an Infant: Serial Cytogenetic and Fetal Hemoglobin Studies

PEDIATRICS ◽  
1966 ◽  
Vol 38 (2) ◽  
pp. 295-299
Author(s):  
GERALD E. BLOOM ◽  
PARK S. GERALD ◽  
LOUIS K. DIAMOND
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Fetal Hemoglobin ◽  
Myelogenous Leukemia ◽  
Adult Type ◽  
Patient Reported ◽  
Cytogenetic Studies

An 8-month-old child is described who showed typical features of the adult type of chronic myelogenous leukemia including the Philadelphia chromosome. As far as known, this is the youngest patient reported with this disease. Serial fetal hemoglobin levels and cytogenetic studies are presented and discussed in terms of their possible relationship to the origin of the two types of chronic myelogenous leukemia found in childhood.

scholarly journals Preferentially expressed genes in chronic myelogenous leukemia

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1218-1225 ◽  
Author(s):  
WM Mars ◽  
DL Florine ◽  
M Talpaz ◽  
GF Saunders
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Circulating Cells ◽  
Patient Screening ◽  
Leukocyte Alkaline Phosphatase ◽  
Acute Myelogenous ◽  
Acute Myelomonocytic Leukemia ◽  
Normal Human

Abstract The predominant circulating cells in chronic myelogenous leukemia (CML) morphologically resemble normal myeloid precursors; however, certain characteristics indicate the two are not identical. Approximately 88% of the patients with clinically typical CML present with a cytogenetic abnormality known as the Philadelphia chromosome (Ph1). Additionally, the leukocyte alkaline phosphatase (LAP) value is decreased in CML. To investigate if there are selected genes expressed in the CML cell population, poly(A+)RNA from a chronic-phase, Ph1-positive CML patient was used for construction of a complementary DNA (cDNA) library. Recombinant clones representing moderately to abundantly transcribed sequences were selected by annealing [32P]-cDNA transcribed from homologous RNA to the library sequences and assessing radioactivity in the hybrids. From an initial 729 colonies, 417 (57.2%) displayed a hybridization signal more intense than controls, indicating these recombinant plasmids contained sequences homologous to moderately or highly expressed RNAs from this particular patient. Screening of the 417 clones--utilizing 32P-cDNAs derived from normal human placenta, an acute myelomonocytic leukemia (AMML), and two other CML samples--was used to select clones likely to represent sequences preferentially expressed in CML. Sixteen recombinants were initially selected that repeatedly failed to display hybridization with the placenta and AMML- derived probes. Further analysis of eight of these clones indicated that six contain sequences preferentially expressed in CML. One clone, C-A3, has been studied with 63 different RNA samples. This sequence is found to be highly expressed in peripheral blood cells from the chronic phase of both Ph1-positive and Ph1-negative CML as well as in a Ph1- positive acute myelogenous leukemia (AML). Expression is reduced in lymphoblastic crisis of CML (L BC-CML) and essentially absent in myeloblastic crisis of CML (M BC-CML). While preliminary, the results suggest that this probe may be useful as an aid in diagnosing Ph1- negative CML and in distinguishing M BC-CML from L BC-CML and Ph1- positive AML.

scholarly journals Preferentially expressed genes in chronic myelogenous leukemia

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1218-1225
Author(s):  
WM Mars ◽  
DL Florine ◽  
M Talpaz ◽  
GF Saunders
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Circulating Cells ◽  
Patient Screening ◽  
Leukocyte Alkaline Phosphatase ◽  
Acute Myelogenous ◽  
Acute Myelomonocytic Leukemia ◽  
Normal Human

The predominant circulating cells in chronic myelogenous leukemia (CML) morphologically resemble normal myeloid precursors; however, certain characteristics indicate the two are not identical. Approximately 88% of the patients with clinically typical CML present with a cytogenetic abnormality known as the Philadelphia chromosome (Ph1). Additionally, the leukocyte alkaline phosphatase (LAP) value is decreased in CML. To investigate if there are selected genes expressed in the CML cell population, poly(A+)RNA from a chronic-phase, Ph1-positive CML patient was used for construction of a complementary DNA (cDNA) library. Recombinant clones representing moderately to abundantly transcribed sequences were selected by annealing [32P]-cDNA transcribed from homologous RNA to the library sequences and assessing radioactivity in the hybrids. From an initial 729 colonies, 417 (57.2%) displayed a hybridization signal more intense than controls, indicating these recombinant plasmids contained sequences homologous to moderately or highly expressed RNAs from this particular patient. Screening of the 417 clones--utilizing 32P-cDNAs derived from normal human placenta, an acute myelomonocytic leukemia (AMML), and two other CML samples--was used to select clones likely to represent sequences preferentially expressed in CML. Sixteen recombinants were initially selected that repeatedly failed to display hybridization with the placenta and AMML- derived probes. Further analysis of eight of these clones indicated that six contain sequences preferentially expressed in CML. One clone, C-A3, has been studied with 63 different RNA samples. This sequence is found to be highly expressed in peripheral blood cells from the chronic phase of both Ph1-positive and Ph1-negative CML as well as in a Ph1- positive acute myelogenous leukemia (AML). Expression is reduced in lymphoblastic crisis of CML (L BC-CML) and essentially absent in myeloblastic crisis of CML (M BC-CML). While preliminary, the results suggest that this probe may be useful as an aid in diagnosing Ph1- negative CML and in distinguishing M BC-CML from L BC-CML and Ph1- positive AML.

Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.

1983 ◽  
Vol 1 (11) ◽  
pp. 669-676 ◽  
Author(s):  
K Jain ◽  
Z Arlin ◽  
R Mertelsmann ◽  
T Gee ◽  
S Kempin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Chronic Myelogenous Leukemia ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Leukocyte Antigen ◽  
Terminal Transferase

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.

Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2733-2740 ◽  
Author(s):  
Baijun Fang ◽  
Chunmei Zheng ◽  
Lianming Liao ◽  
Qin Han ◽  
Zhao Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Progenitor Cells ◽  
Chronic Myelogenous Leukemia ◽  
Blood Cells ◽  
Fusion Gene ◽  
Fetal Liver ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Leukemic Cells

AbstractOverwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. Interestingly, the BCR/ABL fusion gene, which is present in chronic myelogenous leukemia (CML), was also detected in the endothelial cells of patients with CML, suggesting that CML might originate from hemangioblastic progenitor cells that can give rise to both blood cells and endothelial cells. Here we isolated fetal liver kinase-1–positive (Flk1+) cells carrying the BCR/ABL fusion gene from the bone marrow of 17 Philadelphia chromosome–positive (Ph+) patients with CML and found that these cells could differentiate into malignant blood cells and phenotypically defined endothelial cells at the single-cell level. These findings provide direct evidence for the first time that rearrangement of the BCR/ABL gene might happen at or even before the level of hemangioblastic progenitor cells, thus resulting in detection of the BCR/ABL fusion gene in both blood and endothelial cells.

Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3547-3553 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge Cortes ◽  
Susan O'Brien ◽  
Francis J. Giles ◽  
Maher Albitar ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Response Rate ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Blast Phase ◽  
Molecular Abnormalities ◽  
Philadelphia Chromosome Positive

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor [Ph+, 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P = .001), longer median survival (7 versus 4 months, P = .04), and lower 4-week induction mortality (4% versus 15%, P = .07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

scholarly journals Clonal analysis of bcr-abl rearrangement in T lymphocytes from patients with chronic myelogenous leukemia

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
D Jonas ◽  
M Lubbert ◽  
ES Kawasaki ◽  
M Henke ◽  
KJ Bross ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
T Lymphocytes ◽  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Precursor Cell ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
T Cell Clones ◽  
Cell Clones

The cytogenetic hallmark of chronic myelogenous leukemia (CML) is the Philadelphia chromosome (Ph1), which reflects a chromosomal translocation t(9;22) and a rearrangement of the ABL and bcr genes. This marker is found in all cells arising from the same malignant precursor cell and can be detected in CML cells of the myeloid, monocytic, erythroid, and B-lymphocyte lineage. It is, however, controversial as to whether T lymphocytes of CML patients carry this gene rearrangement. An answer to this question would clarify whether the translocation in CML occurs in a pluripotent hematopoietic stem cell or in a precursor cell already committed to certain lineages, but not the T-cell lineage. To address this question, we established T-cell clones from peripheral venous blood cells of four patients with CML and screened these clones for bcr-abl fusion transcripts by means of polymerase chain reaction and Southern blot analysis. In four T-cell clones of three of these patients, the bcr-abl transcript could be detected. None of 12 T-cell clones of the fourth patient disclosed detectable bcr-abl amplification product. Both CD4+ as well as CD8+ clones displayed fused bcr-abl sequences. These data imply that in CML some but not all T lymphocytes may originate from the Ph1-positive stem cell.

scholarly journals Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome

Blood ◽  
1975 ◽  
Vol 45 (3) ◽  
pp. 321-334 ◽  
Author(s):  
CB Lozzio ◽  
BB Lozzio
Keyword(s):  
Cell Line ◽  
Chronic Myelogenous Leukemia ◽  
Culture Media ◽  
Specific Antigen ◽  
Philadelphia Chromosome ◽  
Experimental Studies ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Chromosome 17 ◽  
Leukemia Cell Line

Abstract A cell-line derived from a patient with chronic myelogenous leukemia (CML) is described. The new cell-line, which has over 175 serial passanges in a 3 1/2-yr period, has the following characteristics: (1) CML cells started to proliferate actively since they were first incubated in culture media. A threefold increase in the total number of cells was observed during the first seven passages; the cell population increased by a factor of 10 to 20 every 7 days from passage 8 through 85; from 20 to 40 times from passage 86 through 150, and more than 40 times after 150 passages. (2) The majority of the nononucleated cells are undifferentiated blasts. (3) The karyotype of all the cells examined show the Philadelphia (Ph1) chromosome and a long acrocentric marker plus aneuploidy. The Giemsa-banding studies identified the Ph1 chromosome as a terminal deletion of the long arm of chromosome 22:del(22)(q12) and the long acrocentric marker as an unbalanced reciprocal translocation of one chromosome 17 and the long arm of one chromosome 15. (4) The CML cells do not produce immunoglobulins, are free of mycoplasma, Epstein-Barr virus, and herpes-like virus particles. (5) CML cells have no alkaline phosphatase and myeloperoxidase activities and did not engulf inert particles. (6) Cultured CML cells provide a constant source of a specific antigen. This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies.

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