Early T cell precursor lymphoid blast crisis of chronic myeloid leukemia – A novel transformation

Abstract Chronic myeloid leukemia (CML) is a rare malignancy in children and is mostly diagnosed in the chronic phase (CP). In adults, the five-year overall survival rate is 89% for patients on Imatinib and disease progression occurs in 1-3% per year (Druker 2006). Once a blast crisis (BC) has occurred, treatment options are limited with a median survival of only a few months (Cortes 2008). Therefore, early recognition of patients at risk for developing a BC is desirable. Besides the translocation t(9;22)(q34;q11), IKZF1, PAX5, and CDKN2A deletions have been reported in CML lymphoid blast crisis (LyBC) of both adult and pediatric patients (Mullighan 2008, Alpár 2012). The aim of this study was to investigate the presence of IKZF1 deletions and other copy number alterations (CNAs) by MLPA analysis in a large cohort of pediatric CML patients at time of diagnosis in order to determine whether CNAs commonly found in pediatric ALL might predict disease progression and / or treatment response. Between October 1991 and October 2012 a total of 86 children with newly diagnosed CML were included. The median follow up was 31 months. Among the 86 patients, 82 patients were diagnosed in CP, 2 patients in accelerated phase (AP), and 2 patients in LyBC. Six patients experienced progression to a BC respectively a myeloid blast crisis (MyBC) (N=2) and LyBC (N=4). At time of diagnosis, an IKZF1 deletion was detected in one patient diagnosed with CML-AP (Table A, patient no 58). IKZF1 and EBF1 deletions were detected in one patient diagnosed with CML-LyBC (Table A, patient no 22). No CNAs were detected in the 82 patients diagnosed with CML-CP. At time of disease progression, new CNAs were detected at time of the LyBC (Table A, patient no 62, 64, and 67). Due to the absence of material no CNAs could be detected in both patients experiencing a MyBC. In conclusion, we were able to detect CNAs in progressive CML disease (CML-AP and CML-LyBC) and not in the samples at the time of chronic phase in this large pediatric cohort of CML patients. Therefore, the investigated CNAs could not be used to predict disease progression at time of diagnosis. The CNAs detected in patients with progressive CML were similar to specific CNAs detected in pediatric B-cell precursor ALL, indicating a similar disease development (Kuiper 2010). Additionally, our results are in accordance with existing literature, suggesting that mechanisms of disease progression in pediatric and adult CML might be similar (Brazma, 2007). Disclosures: No relevant conflicts of interest to declare.

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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.

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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.

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Nodal T Cell Blast Crisis in Chronic Myeloid Leukemia

Leukemia & Lymphoma ◽

10.3109/10428190009065845 ◽

2000 ◽

Vol 39 (3-4) ◽

pp. 435-440 ◽

Cited By ~ 4

Author(s):

G. Lucero ◽

V. Birman ◽

E. Colimiodio ◽

C. M. Bertinetti ◽

N. Kotliar ◽

...

Keyword(s):

T Cell ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Blast Crisis

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Blast phase of chronic myeloid leukemia presenting as early T‐cell precursor lymphoblastic leukemia

eJHaem ◽

10.1002/jha2.324 ◽

2021 ◽

Author(s):

Lianqun Qiu ◽

Guilin Tang ◽

Shaoying Li ◽

Wei Wang ◽

Sa A. Wang ◽

...

Keyword(s):

T Cell ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

Cell Precursor ◽

Blast Phase

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T-Cell Blast Crisis in Chronic Myeloid Leukemia

Leukemia & Lymphoma ◽

10.3109/10428199109070275 ◽

1991 ◽

Vol 3 (5-6) ◽

pp. 319-324 ◽

Cited By ~ 2

Author(s):

Keith Stewart ◽

Andre Schuh ◽

Armand Keating

Keyword(s):

T Cell ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Blast Crisis

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

Blood ◽

10.1182/blood.v66.5.1155.1155 ◽

1985 ◽

Vol 66 (5) ◽

pp. 1155-1161 ◽

Cited By ~ 29

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

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.

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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.

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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.

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