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Biotargets of Cancer in Current Clinical Practice pp 159–194Cite as

Leukemias

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Part of the book series: Current Clinical Pathology ((CCPATH))

Abstract

The new understanding of the mechanisms involved in the transformation process and tumor progression, and recognition of oncogenes and proteins involved in regulating these processes, has opened a new era in diagnostic formulation and clinical evaluation of new drugs. The proteins that regulate proliferation, differentiation, apoptosis, and cell invasiveness are the basis of leukemogenesis and are the target of this new therapeutic approach (targeted therapy). The study of some aspects of molecular biology, such as growth factors, molecules involved in signal transduction, angiogenesis, apoptosis, invasiveness, and cell cycle has allowed the identification of new drug targets that interfere with key events of leukemogenesis. Like normal hematopoietic cells, most of the leukemic cells use multiple intracellular signaling pathways to ensure the maintenance of critical functions and activities for their own survival, and these signaling pathways are potential targets for new forms of targeted therapy.

Several novel targeted therapies have recently emerged as active in the treatment of leukemia, including monoclonal antibodies, small molecules that inhibit critical signaling pathways, proapoptotic agents, or modulators of the leukemia microenvironment. Other new agents target novel discovered cell surface receptors or promote DNA damage. Some of these innovative drugs are now commonly used to treat certain leukemias, such as chronic myelogenous leukemia and promyelocytic leukemia. The new lines of research are directed to the identification of pharmacological agents (targeted therapy) that can interfere selectively against specific molecular targets to increase the selectivity of the target and reduce systemic side effects.

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Abbreviations

ABC:

Antibody binding capacity

ADCC:

Antibody-dependent cellular cyto­toxicity

ALL:

Acute lymphoid leukemia

AML:

Acute myeloid leukemia

APL:

Acute promyelocytic leukemia

Ara-C:

Cytarabine

ATO:

Arsenic trioxide

ATRA:

All-trans-retinoic acid

BAALC:

Brain cells and acute leukemia, cytoplasmic

B-CLL:

B-cell chronic lymphocytic leukemia

BCP-ALL:

B-cell precursor acute lymphoblastic leukemia

BCR:

B-cell receptor

cAMP:

Cyclic adenosine monophosphate

CDC:

Complement-dependent cytotoxicity

CDK:

Cyclin-dependent kinase

CLL:

Chronic lymphocytic leukemia

CML:

Chronic myeloid leukemia

CN:

Cytogenetically normal

CR:

Complete remission

ET:

Essential thrombocythemia

EVI1:

Ecotropic viral integration site 1

FCR:

Fludarabine, cyclophosphamide, rituximab

FISH:

Fluorescent in situ hybridization

FLT3:

FMS-like tyrosine kinase 3

GO:

Gemtuzumab ozogamicin

HCL:

Hairy cell leukemia

HDACs:

Histone deacetylases

HIF-1α:

Hypoxia-inducible transcription factor-1 α

HMOX-1:

Heme oxygenase

HSC:

Hematopoietic stem cells

IL:

Interleukin

IFN-α:

Interferon alfa

IgVH:

Immunoglobulin heavy-chain variable gene

IKZF1:

IKAROS family zinc finger 1

ITDs:

Internal tandem duplications

ITIMs:

Immune tyrosine-based inhibitory motifs

LSC:

Leukemic stem cell

MCL:

Mantle cell lymphoma

MDS:

Myelodysplastic syndrome

MESF:

Molecules of equivalent soluble fluorophore

MMPs:

Matrix metalloproteinases

MN1:

Meningioma 1

MoAb:

Monoclonal antibody

MPD:

Myeloproliferative disorder

MPN:

Myeloproliferative neoplasm

NFκB:

Nuclear factor kappa B

NPM1:

Nucleophosmin 1

NRP-1:

Neuropilin-1

NR:

Nonresponder

NRR:

Negative regulatory region

PCD:

Programmed cell death

PCR:

Polymerase chain reaction

Ph-chromosome:

Philadelphia chromosome

PI3K:

Phosphoinositide 3-kinase

PLL:

Prolymphocytic leukemia

PMF:

Primary myelofibrosis

PML-RARα:

Promyelocytic leukemia–retinoic acid receptor-α

PR:

Partial remission

PTD:

Partial tandem duplications

PV:

Polycythemia vera

R:

Responder

RARG:

Retinoic acid receptor-γ

RoS:

Reactive oxygen species

siRNA:

Short-interfering RNA

SLVL:

Splenic lymphoma with villous lymphocytes

SMIPs:

Small-molecule immunophar­maceuticals

T-ALL:

T-lineage ALL

TCRAD:

T-cell receptor α–δ

TCRB:

T-cell receptor β

TH:

T helper

TKIs:

Tyrosine kinase inhibitors

TNF-α:

Tumor necrosis factor-alpha

T-PLL:

T-prolymphocytic leukemia

VDR:

Vitamin D receptor

VEGF:

Vascular endothelial growth factor

WT1:

Wilms tumor 1

XiaP:

X-linked inhibitor of apoptosis

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    Lia Ginaldi M.D. & Massimo De Martinis M.D.

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    Mauro Bologna

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Ginaldi, L., De Martinis, M. (2012). Leukemias. In: Bologna, M. (eds) Biotargets of Cancer in Current Clinical Practice. Current Clinical Pathology. Humana Press. https://doi.org/10.1007/978-1-61779-615-9_6

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