T cell lineage involvement in lymphoid blast crisis of chronic myeloid leukemia

Abstract Cytochemical and immunologic analysis of cells obtained from two patients with chronic myeloid leukemia (CML) during blast crisis reveals markers suggestive of an immature lymphoid phenotype. Peripheral blood mononuclear cells from both patients generated spontaneous lymphoblastoid colonies in methylcellulose, a phenomenon observed in T cell acute lymphoblastic leukemias and T cell non- Hodgkin's lymphomas but not in any other type of leukemia. Colonies derived from one patient were composed predominantly of OKT3+ cells (89%), whereas those from the second patient displayed 42% OKT3+ and OKT6+ cells. In the second patient's colonies, each of five mitoses contained the Philadelphia chromosome (Ph1) and two of five displayed the same additional karyotypic abnormalities as the blast crisis cells. Cells obtained from the two patients during remission still gave rise to spontaneous T cell colonies (greater than 85% OKT3+) and Ph1 was detected in 33% and 60% of the metaphases, respectively. However, when colony growth was induced by an interleukin 2-containing conditioned medium, less than 5% of mitoses were Ph1-positive. These data suggest that: (1) the T cell lineage might be involved in CML; (2) a subset of T cells may remain unaffected by the leukemic process, as demonstrated by the virtual absence of Ph1 in induced T cell colonies; and (3) the spontaneous colony assay seems to select for the growth of malignant T cells.

Download Full-text

T cell lineage involvement in lymphoid blast crisis of chronic myeloid leukemia

Blood ◽

10.1182/blood.v66.5.1155.bloodjournal6651155 ◽

1985 ◽

Vol 66 (5) ◽

pp. 1155-1161 ◽

Cited By ~ 1

Author(s):

M Allouche ◽

A Bourinbaiar ◽

V Georgoulias ◽

R Consolini ◽

A Salvatore ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Blast Crisis ◽

Interleukin 2 ◽

Philadelphia Chromosome ◽

Cell Lineage ◽

Virtual Absence ◽

Hodgkin's Lymphomas

Cytochemical and immunologic analysis of cells obtained from two patients with chronic myeloid leukemia (CML) during blast crisis reveals markers suggestive of an immature lymphoid phenotype. Peripheral blood mononuclear cells from both patients generated spontaneous lymphoblastoid colonies in methylcellulose, a phenomenon observed in T cell acute lymphoblastic leukemias and T cell non- Hodgkin's lymphomas but not in any other type of leukemia. Colonies derived from one patient were composed predominantly of OKT3+ cells (89%), whereas those from the second patient displayed 42% OKT3+ and OKT6+ cells. In the second patient's colonies, each of five mitoses contained the Philadelphia chromosome (Ph1) and two of five displayed the same additional karyotypic abnormalities as the blast crisis cells. Cells obtained from the two patients during remission still gave rise to spontaneous T cell colonies (greater than 85% OKT3+) and Ph1 was detected in 33% and 60% of the metaphases, respectively. However, when colony growth was induced by an interleukin 2-containing conditioned medium, less than 5% of mitoses were Ph1-positive. These data suggest that: (1) the T cell lineage might be involved in CML; (2) a subset of T cells may remain unaffected by the leukemic process, as demonstrated by the virtual absence of Ph1 in induced T cell colonies; and (3) the spontaneous colony assay seems to select for the growth of malignant T cells.

Download Full-text

Characteristics of the TCR Vbeta Repertoire and Identical Clonally Expanded T Cells in Chronic Myeloid Leukemia Patients in Advanced Phase with ABL Mutations

Blood ◽

10.1182/blood.v126.23.5136.5136 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5136-5136

Author(s):

Ling Xu ◽

Yuhong Lu ◽

Jing Lai ◽

Wei Yu ◽

Zhenyi Jin ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Chronic Myeloid Leukemia ◽

Natural Science ◽

Myeloid Leukemia ◽

Research Funding ◽

Blast Crisis ◽

Chronic Phase ◽

Cytotoxic Lymphocyte ◽

Advanced Phase

Abstract Abstract Tumor specific or related antigen cytotoxic lymphocyte (CTL) have been identified in chronic myeloid leukemia patients, however, whether they are constituted by specific type of T cell receptor chains has not been illustrated so far. Previous studies have reported abnormal TCR repertoires and clonally expanded TCR Vβ T cells in chronic myeloid leukemia in chronic phase (CP-CML). In this study, we investigated the distribution and clonality of the TCR Vβ repertoire in 5 CML patients in blast crisis (BC-CML) and one in acceleration phase (AP-CML) with ABL kinase domain mutations (KDMs) including T315I, E255K, F317L+S417Y, Y-253F and L387M+T-315A. Examination of TCR Vβ expression and clonality was performed by reverse transcription-polymerase chain reaction (RT-PCR) combined with GeneScan analysis. Significantly skewed TCR Vβ repertoires were observed in those patients, and 4 to 8 oligoclonally expanded TCR Vβ subfamilies could be identified in each sample, which distributed in 15/24 different subfamilies (TCR Vβ4, Vβ5, Vβ6, β8, Vβ9, Vβ10, Vβ15, Vβ16, Vβ17, Vβ18, Vβ19, Vβ21, Vβ22, Vβ23, Vβ24). Intriguingly, a relatively highly expanded Vβ9 clone with the same length as CDR3 (139 bp) was found in all three CML patients in lymphoid blast crisis (LBC-CML) who had different KDMs, but the clone was not detected in the other two CML patient in myeloid blast crisis (MBC-CML) or the one CML patients in accelerated phase. In conclusion, restricted TCR Vβ repertoire expression and decreased clone complexity was a general phenomenon in the BC-CML patients with different KDMs, indicating the T-cell immunodeficiency status of these patients, and clonally expanded Vβ9 T cell clones may represent a specific immune response to leukemia-associated antigens in LBC-CML patients. Disclosures Li: The Foundation for High-level Talents in Higher Education of Guangdong, China ([2013]246-54),and the Guangzhou Science and Technology Project Foundation (201510010211): Research Funding; National Natural Science Foundation of China (81270604, U1301226, and 81400109), the Guangdong Natural Science Foundation (S2013040016151 and S2013020012863): Research Funding.

Download Full-text

T-cell surface antigens in a patient with blast crisis of chronic myeloid leukemia

Blood ◽

10.1182/blood.v61.4.640.640 ◽

1983 ◽

Vol 61 (4) ◽

pp. 640-644 ◽

Cited By ~ 133

Author(s):

JD Griffin ◽

R Tantravahi ◽

GP Canellos ◽

JS Wisch ◽

EL Reinherz ◽

...

Keyword(s):

T Cell ◽

Chronic Myeloid Leukemia ◽

Cell Surface ◽

Myeloid Leukemia ◽

Blast Crisis ◽

Philadelphia Chromosome ◽

Chromosome Analysis ◽

Surface Antigens ◽

Cell Surface Antigens ◽

Clone Cells

Abstract There is little evidence to suggest that T lymphocytes are involved in the leukemic process in chronic myeloid leukemia (CML). A case of CML in blast phase is described in which T-cell surface antigens were detected by immunofluorescence on the patient's blasts using monoclonal antibodies. In order to determine that the T-cell blasts were derived from the original CML clone, cells bearing the T3 antigen were isolated by fluorescence-activated cell sorting and chromosome analysis was performed. All metaphases examined had the Philadelphia chromosome, confirming their origin from CML.

Download Full-text

T-cell surface antigens in a patient with blast crisis of chronic myeloid leukemia

Blood ◽

10.1182/blood.v61.4.640.bloodjournal614640 ◽

1983 ◽

Vol 61 (4) ◽

pp. 640-644 ◽

Cited By ~ 1

Author(s):

JD Griffin ◽

R Tantravahi ◽

GP Canellos ◽

JS Wisch ◽

EL Reinherz ◽

...

Keyword(s):

T Cell ◽

Chronic Myeloid Leukemia ◽

Cell Surface ◽

Myeloid Leukemia ◽

Blast Crisis ◽

Philadelphia Chromosome ◽

Chromosome Analysis ◽

Surface Antigens ◽

Cell Surface Antigens ◽

Clone Cells

There is little evidence to suggest that T lymphocytes are involved in the leukemic process in chronic myeloid leukemia (CML). A case of CML in blast phase is described in which T-cell surface antigens were detected by immunofluorescence on the patient's blasts using monoclonal antibodies. In order to determine that the T-cell blasts were derived from the original CML clone, cells bearing the T3 antigen were isolated by fluorescence-activated cell sorting and chromosome analysis was performed. All metaphases examined had the Philadelphia chromosome, confirming their origin from CML.

Download Full-text

Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome

New England Journal of Medicine ◽

10.1056/nejm200104053441402 ◽

2001 ◽

Vol 344 (14) ◽

pp. 1038-1042 ◽

Cited By ~ 1916

Author(s):

Brian J. Druker ◽

Charles L. Sawyers ◽

Hagop Kantarjian ◽

Debra J. Resta ◽

Sofia Fernandes Reese ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Chronic Myeloid Leukemia ◽

Tyrosine Kinase ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

Blast Crisis ◽

Philadelphia Chromosome ◽

Specific Inhibitor ◽

Abl Tyrosine Kinase

Download Full-text

Pathological Fracture: An Unusual Presentation in Childhood Chronic Myeloid Leukemia

Indonesian Journal of Cancer ◽

10.33371/ijoc.v13i4.675 ◽

2019 ◽

Vol 13 (4) ◽

pp. 140

Author(s):

Mururul Aisyi ◽

Ayu Hutami Syarif ◽

Anita Meisita ◽

Agus Kosasih ◽

Achmad Basuki ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Pathological Fracture ◽

Hematological Malignancy ◽

Blast Crisis ◽

Philadelphia Chromosome ◽

Molecular Response ◽

Invasive Treatment ◽

Non Invasive ◽

Blast Count

Introduction: Chronic Myeloid Leukemia is a hematological malignancy driving from myeloproliferative process. It is typified by the presence of the Philadelphia chromosome manifesting in certain distinct complications, including pathological fracture. Pathological fracture is recognized as an extramedullary disease that occurs as a result of transformation of CML into blast crisis phase.Case Presentation: Here, we report a case of pediatric male CML. After being failed with imatinib therapy, he turned to nilotinib and was unable to achieve a major molecular response. He presented with high blast count and pain in the left arm. He was diagnosed with pathological fracture and blast crisis phase CML. Taken the young age and displacement of fracture into consideration, he was conservatively treated by a combination of immobilization and a higher dose of targeted therapy, nilotinib. The 2-month evaluation revealed clinical union and reduction of blast cells.Conclusions: Regarding the minimal displacement and age presentation, pathological fracture in pediatric CML requires non-invasive treatment and optimization of antileukemic therapy.

Download Full-text

Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis

Blood ◽

10.1182/blood.v84.12.4322.bloodjournal84124322 ◽

1994 ◽

Vol 84 (12) ◽

pp. 4322-4332 ◽

Cited By ~ 29

Author(s):

P Valent ◽

E Spanblochl ◽

HC Bankl ◽

WR Sperr ◽

C Marosi ◽

...

Keyword(s):

Mast Cell ◽

Growth Factor ◽

Mast Cells ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Blast Crisis ◽

Cell Lineage ◽

Kit Ligand ◽

Mast Cell Growth Factor

Autonomous, factor-independent growth and differentiation of malignant cells in preleukemic and leukemic disease states is a well-recognized phenomenon and is often associated with a poor prognosis. Mast cells are distinct hematopoietic cells and express a unique profile of antigens. Growth and differentiation of normal mast cells is dependent on mast cell growth factor (MGF), the ligand of the c-kit protooncogene product. In this study, we screened for mast cell-lineage involvement in 52 patients suffering from myeloid leukemias, myelodysplastic syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit ligand/MGF-independent growth of mast cells in long-term suspension culture. Of the 52 patients tested, 2 patients with refractory anemia with excess of blast cells in transformation and 1 patient suffering from chronic myeloid leukemia blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells expressed the mast-cell-related surface antigen c-kit, but not basophil-related antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture. No autocrine production, paracrine production, or overproduction of MGF was found. The spontaneous growth of mast cells could neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent differentiation of mast cells in these patients could be abbrogated by MoAbs to c-kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels in these patients were within the normal range and MGF could not be detected in cell-free culture supernatants. All 3 patients showed rapid progression of disease and had a survival time of less than 1 year. In conclusion, we describe a unique form of transformation in MDS and CML-BC characterized by mast cell lineage involvement and factor-independent differentiation of mast cells. This form of leukemic transformation has to be delineated from chronic myeloid leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and from monocytic leukemias and myelodysplastic disorders associated with basophilia.

Download Full-text

Basophils (Bsp-1+) derive from the leukemic clone in human myeloid leukemias involving the chromosome breakpoint 9q34

Blood ◽

10.1182/blood.v73.3.777.777 ◽

1989 ◽

Vol 73 (3) ◽

pp. 777-781 ◽

Cited By ~ 12

Author(s):

MP Bodger ◽

CM Morris ◽

MA Kennedy ◽

JA Bowen ◽

JM Hilton ◽

...

Keyword(s):

Toluidine Blue ◽

Myeloid Leukemia ◽

Blast Crisis ◽

Interleukin 2 ◽

Philadelphia Chromosome ◽

Chronic Phase ◽

Normal Karyotype ◽

Buffy Coat ◽

Chromosome 9 ◽

Leukemic Clone

Abstract The monoclonal antibody (MoAb) Bsp-1 was used to purify basophilic cells from leukemic blood of five patients with Philadelphia chromosome (Ph′) positive chronic myeloid leukemia (CML) and two patients with acute myeloid leukemia (AML) characterized by the chromosomal translocation t(6;9)(p23;q34). When cultured, Bsp-1 positive cells from all CML and AML patients showed the same clonal karyotype changes observed in diagnostic buffy coat preparations, indicating that the basophilic cells were of leukemic origin. In contrast, T lymphocytes from four of five CML patients cultured in the presence of interleukin- 2 (IL-2) showed a normal karyotype and were therefore not derived from the leukemic clone. Bsp-1 staining correlated with toluidine blue- positive basophils in chronic phase CML and with toluidine blue- negative blast cells expressing an immature myeloid phenotype in blast crisis CML and AML. Chromosome in situ hybridization showed that the ABL oncogene was translocated from chromosome 9 to chromosome 22 in the CML patients but remained on chromosome 9 in the AML patients. These results indicate that the breakpoint at 9q34 in CML is 5′ of ABL, whereas the breakpoint at 9q34 in AML is 3′ of ABL. Field inversion gel electrophoresis showed that the 9q34 breakpoint was not within 200 kb 3′ of ABL in one of the AML patients, nor was there any rearrangement of the PIM oncogene locus at 6p21.

Download Full-text