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.

An Unusual Case of Philadelphia Chromosome–Positive Chronic Myelogenous Leukemia With Trisomy 19 Presenting With Megakaryoblastosis and Myelofibrosis

2013 ◽  
Vol 137 (8) ◽  
pp. 1147-1151 ◽  
Author(s):  
Nika Aljinovic ◽  
Agata M. Bogusz ◽  
Sibel Kantarci ◽  
Thomas P. Buck ◽  
Rajan Dewar
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Life Saving ◽  
Cytogenetic Studies ◽  
Night Sweats ◽  
Infectious Etiology

Initial identification of chronic myelogenous leukemia is very important since targeted therapy leads to life-saving remission. Rarely, chronic myelogenous leukemia presents with an unusual picture, making the diagnosis challenging. We describe such a case of chronic myelogenous leukemia in blast crisis in a previously healthy 61-year-old woman. The patient presented with fever, myalgias, and night sweats and was first worked up for an infectious etiology. Because of persistent anemia, a bone marrow biopsy was performed that revealed fibrosis with increased megakaryoblasts. Even though initial cytogenetic studies could not be performed because of “dry tap” aspirate, persistent efforts for cytogenetic studies were made, including a “squeeze preparation” from the core biopsy, which revealed t(9;22)(q34;q11.2) and trisomy 19. The patient was treated with tyrosine kinase inhibitors, chemotherapy, and subsequently an allogeneic stem cell transplant. She is in persistent remission. This case illustrates a complex presentation of chronic myelogenous leukemia and provides an overview of morphologic cues and the importance of performing cytogenetic studies that led to the diagnosis.

Lymphoblastic Conversion in Chronic Myelogenous Leukemia

PEDIATRICS ◽  
1978 ◽  
Vol 61 (4) ◽  
pp. 560-563
Author(s):  
William M. Crist ◽  
Abdelsalam H. Ragab ◽  
Rafael Ducos
Keyword(s):  
Acute Leukemia ◽  
Chronic Myelogenous Leukemia ◽  
Growth Parameters ◽  
Philadelphia Chromosome ◽  
Soft Agar ◽  
Myelogenous Leukemia ◽  
Adult Type ◽  
Agar Culture ◽  
Blast Cells ◽  
Culture Growth

A child presented with "acute leukemia" in which the blast cells resembled lymphoblasts and had negative cytochemical staining (PAS, Sudan black, and myeloperoxidase). Remission was induced and typical adult-type chronic myelogenous leukemia (CML) followed. Cytogenetic studies initially and during remission and subsequent "acute leukemia" relapses revealed the presence of the Philadelphia chromosome abnormality. Terminal transferase assay performed on peripheral blood blast cells was markedly elevated and soft agar culture growth parameters were typical of acute lymphohlastic leukemia. T and B cell marker studies revealed no markers. This case report with supportive laboratory studies suggests that a cell line with lymphoid characteristics may predominate during acute leukemic transformation. This type of subclassification of leukemia may be of importance in therapeutic planning.

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.

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 Association of the translocation (15;17) with malignant proliferation of promyelocytes in acute leukemia and chronic myelogenous leukemia at blastic crisis

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 270-274 ◽  
Author(s):  
S Misawa ◽  
E Lee ◽  
CA Schiffer ◽  
Z Liu ◽  
JR Testa
Keyword(s):  
Bone Marrow ◽  
Chronic Myelogenous Leukemia ◽  
Bone Marrow Cells ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Blastic Crisis ◽  
Cytogenetic Studies ◽  
Chromosomal Breakpoints ◽  
Variant Translocation ◽  
Marrow Cells

Abstract Cytogenetic studies were performed on nine patients with acute promyelocytic leukemia. Every patient had an identical translocation (15;17) or, in one case, a variant three-way rearrangement between chromosomes 7, 15, and 17. Another patient with chronic myelogenous leukemia was examined at the time of blastic crisis when the patient's bone marrow was infiltrated by hypergranular promyelocytes and blasts. Bone marrow cells contained a t(15;17) as well as a Ph1 chromosome. Only the latter abnormality was observed in the chronic phase of the disease. The translocation (15;17) was detected in all ten patients when bone marrow or peripheral blood cells were cultured for 24 hours prior to making chromosome preparations. However, the t(15;17) was not seen in three of these same cases when bone marrow cells were processed directly. These findings indicate that the t(15;17) is closely associated with acute proliferation of leukemic promyelocytes and that detection of this karyotypic defect may be influenced by the particular cytogenetic processing method used in different laboratories. An analysis of the banding pattern in the variant translocation provided additional evidence favoring chromosomal breakpoints at or very near the junction between bands 17q12 and 17q21 and at 15q22.

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.

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