Leukemia-associated antigens in ALL

A cytotoxic common ALL antiserum (CALLA) specific for leukemic cells of most patients with non-T-cel- acute lymphoblastic leukemia (ALL) and of some patients with chronic myelogenous leukemia (CML) in blast crisis has been reproducibly prepared using cell lines for absorption. CALLA reacts with leukemic cells of 110 of 134 patients (82%) with non-T-cell ALL; 1 of 71 (1%) patients with acute myelogenous leukemia (AML); 2 of 7 patients (29%) with chronic myelogenous leukemia in blast crisis; 7 of 92 patients (8%) with other hematologic malignancies; and with the leukemic cell lines Laz 221 and NALM-1. It does not react with the normal hematopoietic cells, B- or T-cell lines, or cells from 26 patients with T-cell ALL that were tested. CALLA reactivity and periodic acid Schiff (PAS) staining correlate poorly, with CALLA reacting with cells from 86% (64 of 74) of patients with PAS-positive and 76% (29 of 38) of those with PAS-negative non-T-cell ALL. In these patients, CALLA reacts with cells from 89% of those under age 12 (78 of 88); 74% of those aged 12--20 (20 of 27); and 58% of those over 20 (11 of 19). Using only CALLA and antisera specific for Ia-like and T-cell antigens, we can now distinguish most cases of ALL from AML and other hematologic malignancies.

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Leukemia-associated antigens in ALL

Blood ◽

10.1182/blood.v54.6.1240.1240 ◽

1979 ◽

Vol 54 (6) ◽

pp. 1240-1248 ◽

Cited By ~ 38

Author(s):

JM Pesando ◽

J Ritz ◽

H Lazarus ◽

SB Costello ◽

S Sallan ◽

...

Keyword(s):

T Cell ◽

Cell Lines ◽

Chronic Myelogenous Leukemia ◽

Lymphoblastic Leukemia ◽

Blast Crisis ◽

Periodic Acid ◽

Hematologic Malignancies ◽

Myelogenous Leukemia ◽

Leukemic Cells ◽

Periodic Acid Schiff

Abstract A cytotoxic common ALL antiserum (CALLA) specific for leukemic cells of most patients with non-T-cel- acute lymphoblastic leukemia (ALL) and of some patients with chronic myelogenous leukemia (CML) in blast crisis has been reproducibly prepared using cell lines for absorption. CALLA reacts with leukemic cells of 110 of 134 patients (82%) with non-T-cell ALL; 1 of 71 (1%) patients with acute myelogenous leukemia (AML); 2 of 7 patients (29%) with chronic myelogenous leukemia in blast crisis; 7 of 92 patients (8%) with other hematologic malignancies; and with the leukemic cell lines Laz 221 and NALM-1. It does not react with the normal hematopoietic cells, B- or T-cell lines, or cells from 26 patients with T-cell ALL that were tested. CALLA reactivity and periodic acid Schiff (PAS) staining correlate poorly, with CALLA reacting with cells from 86% (64 of 74) of patients with PAS-positive and 76% (29 of 38) of those with PAS-negative non-T-cell ALL. In these patients, CALLA reacts with cells from 89% of those under age 12 (78 of 88); 74% of those aged 12--20 (20 of 27); and 58% of those over 20 (11 of 19). Using only CALLA and antisera specific for Ia-like and T-cell antigens, we can now distinguish most cases of ALL from AML and other hematologic malignancies.

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A Rare Case of Chronic Myelogenous Leukemia Presenting as T-Cell Lymphoblastic Crisis

Case Reports in Oncological Medicine ◽

10.1155/2018/7276128 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

Parikshit Padhi ◽

Margarita Topalovski ◽

Radwa El Behery ◽

Eduardo S. Cantu ◽

Ramadevi Medavarapu

Keyword(s):

Stem Cell ◽

T Cell ◽

Chronic Myelogenous Leukemia ◽

Stem Cell Transplant ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Blast Crisis ◽

Myelogenous Leukemia ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant

Chronic Myelogenous Leukemia in blast crisis can manifest as either myeloid (more common) or lymphoid blast crisis. Most lymphoblastic crises are of B-cell lineage. T-cell blast crisis is extremely rare, with only a few reported cases. We present a case of a middle-aged man who was diagnosed with CML on peripheral blood and bone marrow biopsy. Because of a generalized lymphadenopathy noted at the time of diagnosis, a lymph node biopsy was also performed, which revealed a T-cell lymphoblastic leukemia/lymphoma, BCR/ABL1 positive, with clonal evolution. This is a very rare manifestation of CML in blast crisis with no standard treatment and with poor outcomes despite chemotherapy or allogeneic stem cell transplant. Given its rarity, it would be difficult to develop standard chemotherapy protocols. We believe the treatment for this condition should be similar to any lymphoid blast crisis. The patient was treated with induction chemotherapy (hyper-CVAD regimen) plus dasatinib for 3 cycles followed by sibling-donor allogeneic stem cell transplant and is currently on maintenance dasatinib and has minimal residual disease at this time.

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The receptor tyrosine kinase p185HER2 is expressed on a subset of B- lymphoid blasts from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia

Blood ◽

10.1182/blood.v86.5.1916.bloodjournal8651916 ◽

1995 ◽

Vol 86 (5) ◽

pp. 1916-1923 ◽

Cited By ~ 23

Author(s):

HJ Buhring ◽

I Sures ◽

B Jallal ◽

FU Weiss ◽

FW Busch ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Tyrosine Kinase ◽

Cell Lines ◽

Receptor Tyrosine Kinase ◽

Lymphoblastic Leukemia ◽

Blast Crisis ◽

Hematopoietic Cell ◽

Myelogenous Leukemia ◽

Leukemic Cells ◽

B Lymphoid

The class I receptor tyrosine kinase (RTK) HER2 is an oncoprotein that is frequently involved in the pathogenesis of tumors of epithelial origin. Here we report mRNA expression in peripheral blood and bone marrow cells from healthy donors in hematopoietic cell lines and leukemic blasts from patients with acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoblastic leukemia (CLL), and chronic myeloid leukemia (CML). However, cell surface expression of HER2 protein (p185HER2) was found exclusively on a subset of leukemic cells of the B-lymphoblastic lineage. p185HER2 expression was found on blasts in 2 of 15 samples from infants, 9 of 19 samples from adult patients with C-ALL (CD19+CD10+), and 1 of 2 samples from patients with pro-B ALL (CD19+CD10-), whereas none of the leukemic cells from patients with AML (0/30), T-ALL (0/7), CLL (0/5) (CD19+CD5+), or CML in chronic and accelerated phase (0/5) or in blast crisis with myeloid differentiation (0/14) were positive for p185HER2. However, cells from 3 of 4 patients with CML in B-lymphoid blast crisis (CD19+CD10+) expressed high levels of p185HER2, which was also found on the surface of the CML-derived B-cell lines BV-173 and Nalm-1. Our study shows p185HER2 expression on malignant cells of hematopoietic origin for the first time. Aberrant expression of this oncogenic receptor tyrosine kinase in hematopoietic cell types may be an oncogenic event contributing to the development of a subset of B- lymphoblastic leukemias.

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Alternative TEL-JAK2 fusions associated with T-cell acute lymphoblastic leukemia and atypical chronic myelogenous leukemia dissected in zebrafish

Haematologica ◽

10.3324/haematol.2012.064659 ◽

2012 ◽

Vol 97 (12) ◽

pp. 1895-1903 ◽

Cited By ~ 23

Author(s):

S. M. N. Onnebo ◽

P. Rasighaemi ◽

J. Kumar ◽

C. Liongue ◽

A. C. Ward

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Chronic Myelogenous Leukemia ◽

Lymphoblastic Leukemia ◽

Myelogenous Leukemia ◽

Cell Acute Lymphoblastic Leukemia

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Genomic instability of microsatellite repeats and its association with the evolution of chronic myelogenous leukemia [see comments]

Blood ◽

10.1182/blood.v83.12.3449.3449 ◽

1994 ◽

Vol 83 (12) ◽

pp. 3449-3456 ◽

Cited By ~ 90

Author(s):

C Wada ◽

S Shionoya ◽

Y Fujino ◽

H Tokuhiro ◽

T Akahoshi ◽

...

Keyword(s):

Genomic Instability ◽

Chronic Myelogenous Leukemia ◽

Blast Crisis ◽

Chronic Phase ◽

Genetic Alterations ◽

Myelogenous Leukemia ◽

Leukemic Cells ◽

Genetic Event ◽

Familial Predisposition ◽

Somatic Instability

Abstract Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor-suppressor genes. Investigation of genomic instability of microsatellites has indicated a new mechanism for human carcinogenesis in hereditary nonpolyposis colorectal cancer and sporadic cancer and this instability has been shown to be related to inherited predisposition to cancer. This study was conducted to determine whether such microsatellite instability is associated with the evolution of chronic myelogenous leukemia (CML) to the blast crisis. Nineteen CML patients clinically progressing from the chronic phase to accelerated phase or blast crisis and 20 other patients in the CML chronic phase were studied. By polymerase chain reaction assay, DNAs for genomic instability in five separate microsatellites in chromosome arms 5q (Mfd27), 17p (Mfd41), 18q (DCC), 3p (CI3–9), and 8p (LPL) were examined. Differences in unrelated microsatellites of chronic and blastic phase DNAs in 14 of 19 patients (73.7%) were demonstrated. Somatic instability in five microsatellites, Mfd27, Mfd41, DCC, CI3–9, and LPL, was detected in 2 of 19 (10.5%), 8 of 19 (42.1%), 11 of 19 (57.9%), 4 of 17 (23.5%), and 4 of 17 (23.5%) cases. In 10 of 19 cases (52.6%), genetic instability in at least two of five microsatellites was observed and was categorized as replication error (RER+) phenotype. CML evolution cases with myeloid, lymphoid, and mixed phenotypes and the blast crisis and accelerated phase showed somatic instability in a number of microsatellites. No alterations in leukemic cells at the chronic phase could be detected in any microsatellites. These data indicate instability of microsatellites (RER+) but not familial predisposition to possibly be a late genetic event in the evolution of CML to blast crisis. In the microsatellite of the DCC gene, complicated alterations in band patterns caused by instability as well as loss of heterozygosity (LOH) were observed in 13 of 19 cases (68.4%): instability in 9 cases, instability plus LOH in 2 cases, and only LOH in 2 cases. These highly frequent alterations in microsatellites, including instability and LOH, suggesting that secondary events due possibly to loss of fidelity in replication and repair machinery may be significantly associated with CML evolution.

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Terminal deoxynucleotidyl transferase activities in human blood leukocytes and lymphoblast cell lines: high levels in lymphoblast cell lines and in blast cells of some patients with chronic myelogenous leukemia in acute phase

Blood ◽

10.1182/blood.v47.1.11.11 ◽

1976 ◽

Vol 47 (1) ◽

pp. 11-20 ◽

Cited By ~ 126

Author(s):

PS Sarin ◽

PN Anderson ◽

RC Gallo

Keyword(s):

T Cell ◽

Cell Lines ◽

Chronic Myelogenous Leukemia ◽

Human Blood ◽

Lymphocytic Leukemia ◽

Myelogenous Leukemia ◽

Thymus Gland ◽

Terminal Deoxynucleotidyl Transferase ◽

Blast Phase ◽

Blast Cells

Abstract Terminal deoxynucleotidyl transferase, an enzyme which catalyzes the polymerization of deoxyribonucleoside triphosphates, elongating oligo- or polydeoxynucleotide chains, but without direction from a nucleic acid template, is thought to be specific for thymus gland and thymus- derived cells. We have confirmed the observations that high levels are characteristic of thymus gland with both human and calf tissue and that elevated levels may be found in some cases of acute lymphocytic leukemia. High levels were also found in human lymphoblast cell lines with T-cell characteristics, and insignificant activity was observed in leukocytes of patients with chronic myelogenous leukemia not in acute blast phase of the disease, chronic lymphocytic leukemia, human B- cells, and normal human blood lymphocytes even after stimulation with phytohemagglutinin. However, high levels (approximately 200 nmoles/hr/10(9) cells) equivalent to those in thymus tissue and lymphoblast cell lines with T-cell characteristics were found in the peripheral blood blast cells of four patients with chronic myelogenous leukemia in an acute blast phase of their disease. One hypothesis that may explain the present results is that in chronic myelogenous leukemia in acute blast phase of the disease the proliferative blast response may not always be myeloblasts but in some cases it may be lymphoblasts.

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Constitutive expression of SOCS3 confers resistance to IFN-α in chronic myelogenous leukemia cells

Blood ◽

10.1182/blood-2002-01-0073 ◽

2002 ◽

Vol 100 (8) ◽

pp. 2926-2931 ◽

Cited By ~ 67

Author(s):

Ikuya Sakai ◽

Kazuto Takeuchi ◽

Hayato Yamauchi ◽

Hirosi Narumi ◽

Shigeru Fujita

Keyword(s):

Cell Line ◽

Cell Lines ◽

Chronic Myelogenous Leukemia ◽

Blast Crisis ◽

Constitutive Expression ◽

Myelogenous Leukemia ◽

Cytokine Signaling ◽

Interferon Α ◽

Socs3 Expression ◽

Blast Cells

Because suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling, it has been hypothesized that aberrant SOCS expression confers resistance against cytokine therapy. This study reports on the constitutive expression of SOCS3 in most chronic myelogenous leukemia (CML) cell lines, which are resistant to treatment with interferon α (IFN-α). In contrast, the KT-1/A3 cell line, in which constitutive expression of SOCS3 is barely detectable, is sensitive to IFN-α treatment. Forced expression of SOCS3 in the KT-1/A3 cell line confers resistance to IFN-α treatment. Furthermore, most of the blast cells from patients in CML blast crisis, which are usually resistant to IFN-α therapy, showed constitutive expression of SOCS3. These findings indicate that constitutive SOCS3 expression affects the IFN-α sensitivity of CML cell lines and blast cells from patients with CML blast crisis.

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Adoptive T-Cell Therapy for B-Cell Acute Lymphoblastic Leukemia: Preclinical Studies

Blood ◽

10.1182/blood.v94.10.3531.422k14_3531_3540 ◽

1999 ◽

Vol 94 (10) ◽

pp. 3531-3540 ◽

Cited By ~ 22

Author(s):

Angelo A. Cardoso ◽

J. Pedro Veiga ◽

Paolo Ghia ◽

Hernani M. Afonso ◽

W. Nicholas Haining ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

T Cell ◽

B Cell ◽

Cell Lines ◽

Lymphoblastic Leukemia ◽

Adoptive T Cell Therapy ◽

Leukemic Cells ◽

Acute Leukemias ◽

T Cell Lines

We have previously shown that leukemia-specific cytotoxic T cells (CTL) can be generated from the bone marrow of most patients with B-cell precursor acute leukemias. If these antileukemia CTL are to be used for adoptive immunotherapy, they must have the capability to circulate, migrate through endothelium, home to the bone marrow, and, most importantly, lyse the leukemic cells in a leukemia-permissive bone marrow microenvironment. We demonstrate here that such antileukemia T-cell lines are overwhelmingly CD8+ and exhibit an activated phenotype. Using a transendothelial chemotaxis assay with human endothelial cells, we observed that these T cells can be recruited and transmigrate through vascular and bone marrow endothelium and that these transmigrated cells preserve their capacity to lyse leukemic cells. Additionally, these antileukemia T-cell lines are capable of adhering to autologous stromal cell layers. Finally, autologous antileukemia CTL specifically lyse leukemic cells even in the presence of autologous marrow stroma. Importantly, these antileukemia T-cell lines do not lyse autologous stromal cells. Thus, the capacity to generate anti–leukemia-specific T-cell lines coupled with the present findings that such cells can migrate, adhere, and function in the presence of the marrow microenvironment enable the development of clinical studies of adoptive transfer of antileukemia CTL for the treatment of ALL.

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NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia

Journal of Experimental Medicine ◽

10.1084/jem.20100745 ◽

2010 ◽

Vol 207 (10) ◽

pp. 2141-2156 ◽

Cited By ~ 40

Author(s):

Sophie Kusy ◽

Bastien Gerby ◽

Nicolas Goardon ◽

Nathalie Gault ◽

Federica Ferri ◽

...

Keyword(s):

T Cell ◽

Tumor Suppressor ◽

Cell Lines ◽

Lymphoblastic Leukemia ◽

Notch Pathway ◽

Gene Promoter ◽

Leukemic Cells ◽

Regulatory Sequence ◽

Human T Cell ◽

T Cell Leukemogenesis

TAL1 (also known as SCL) is expressed in >40% of human T cell acute lymphoblastic leukemias (T-ALLs). TAL1 encodes a basic helix-loop-helix transcription factor that can interfere with the transcriptional activity of E2A and HEB during T cell leukemogenesis; however, the oncogenic pathways directly activated by TAL1 are not characterized. In this study, we show that, in human TAL1–expressing T-ALL cell lines, TAL1 directly activates NKX3.1, a tumor suppressor gene required for prostate stem cell maintenance. In human T-ALL cell lines, NKX3.1 gene activation is mediated by a TAL1–LMO–Ldb1 complex that is recruited by GATA-3 bound to an NKX3.1 gene promoter regulatory sequence. TAL1-induced NKX3.1 activation is associated with suppression of HP1-α (heterochromatin protein 1 α) binding and opening of chromatin on the NKX3.1 gene promoter. NKX3.1 is necessary for T-ALL proliferation, can partially restore proliferation in TAL1 knockdown cells, and directly regulates miR-17-92. In primary human TAL1-expressing leukemic cells, the NKX3.1 gene is expressed independently of the Notch pathway, and its inactivation impairs proliferation. Finally, TAL1 or NKX3.1 knockdown abrogates the ability of human T-ALL cells to efficiently induce leukemia development in mice. These results suggest that tumor suppressor or oncogenic activity of NKX3.1 depends on tissue expression.

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