Myeloid Proliferations and Neoplasms

Myeloid proliferations and neoplasms encompass a diverse group of hematological disorders characterized by abnormal growth and differentiation of myeloid cells. These conditions pose significant challenges in understanding their pathogenesis, identifying therapeutic targets, and developing effective therapies. At our company, we are at the forefront of providing comprehensive drug and therapy development services for myeloid proliferations and neoplasms.

Overview of Myeloid Proliferations and Neoplasms

Myeloid proliferations and neoplasms are a collection of disorders characterized by the peculiar phenomenon of abnormal proliferation and differentiation of myeloid cells, encompassing the likes of granulocytes, monocytes, erythrocytes, and megakaryocytes. It appears that genetic alterations and the unruly dysregulation of signaling pathways play significant roles in driving the abnormal growth and behavior of these myeloid cells. In addition to the key gene BCR-ABL1, other genetic mutations, such as JAK2, MPL, and CALR, have been identified in PV, ET, and PMF. These mutations activate the JAK-STAT signaling pathway, leading to aberrant cell growth and increased production of blood cells.

Fig.1 Examples of histological features of myeloid proliferation and neoplasm diseases. (Pizzi, Marco, et al., 2021)

Classification of Myeloid Proliferations and Neoplasms

Myeloid precursor lesion
- clonal cytopenias of undetermined significance
- clonal hematopoiesis

Myeloproliferative neoplasms
- chronic myeloid leukemia
- chronic neutrophilic leukemia
- chronic eosinophilic leukemia
- polycythemia vera
- essential thrombocythemia
- primary myelofibrosis
- juvenile myelomonocytic leukemia
- myeloproliferative neoplasm, NOS

Mastocytosis
- mastocytosis
- cutaneous mastocytosis
- systemic mastocytosis
- mast cell sarcoma

Myelodysplastic neoplasms
- myelodysplastic neoplasms, with defining genetic abnormalities
  
  -low blasts and SF3B1 mutation
  
  -low blasts and 5q deletion
  
  -biallelic TP53 inactivation
- myelodysplastic neoplasms, morphologically defined
  
  -low blasts
  
  -hypoplastic
  
  -increased blasts
- myelodysplastic neoplasms of childhood
  
  -low blasts
  
  -increased blasts

Myelodysplastic/myeloproliferative neoplasms
- chronic myelomonocytic leukemia
- myelodysplastic / myeloproliferative neoplasm
  
  -neutrophilia
  
  -SF3B1 mutation and thrombocytosis
  
  -NOS

Acute myeloid leukemia
- acute myeloid leukemia with defining genetic abnormalities
  -acute promyelocytic leukemia with PML::RARA fusion
  -acute myeloid leukemia
- RUNX1::RUNX1T1 fusion
- CBFB::MYH11 fusion
- DEK::NUP214 fusion
- RBM15::MRTFA fusion
- BCR::ABL1 fusion
- KMT2A rearrangement
- MECOM rearrangement
- NUP98 rearrangement
- NPM1 mutation
- CEBPA mutation
- myelodysplasia-related
- other defined genetic alterations

acute myeloid leukemia, defined by differentiation
-acute myeloid leukemia with minimal differentiation (without maturation / with maturation)
-acute basophilic / myelomonocytic / monocytic / erythroid / megakaryoblastic leukemia
acute megakaryoblastic leukemia / acute lymphoblastic leukemia / ETP-ALL
myeloid sarcoma

Myeloid neoplasms, secondary
- myeloid neoplasm post cytotoxic therapy
- myeloid neoplasms associated with germline predisposition
- myeloid proliferations associated with Down syndrome

Myeloid/lymphoid neoplasms
myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement

-PDGFRA rearrangement

-PDGFRB rearrangement

-FGFR1 rearrangement

-JAK2 rearrangement

-FLT3 rearrangement

-ETV6::ABL1 fusion

-other tyrosine kinase gene fusions

Acute leukaemias of mixed or ambiguous lineage
- acute leukemia of ambiguous lineage with defining genetic abnormalities
  
  -mixed-phenotype acute leukemia with BCR::ABL1 fusion
  
  -mixed-phenotype acute leukemia with KMT2A rearrangement
  
  -acute leukemia of ambiguous lineage with other defined genetic alterations
  
  -acute leukemia of ambiguous lineage, immunophenotypically defined
  
  -mixed-phenotype acute leukemia, B/myeloid, or T/myeloid, or rare types
  
  -acute leukemia of ambiguous lineage, NOS
  
  -acute undifferentiated leukemia

Therapy Development of Myeloid Proliferations and Neoplasms

Tyrosine kinase inhibitors (TKIs)

The advent of TKIs has heralded a new era in CML. Medications such as imatinib, nilotinib, and dasatinib have brought about a revolution in combating this disease by selectively targeting the BCR-ABL1 fusion protein. These remarkable inhibitors display an impressive ability to suppress the abnormal proliferation of myeloid cells, ultimately leading to profound and long-lasting molecular responses.

JAK inhibitors

For PV, ET, and PMF diseases harboring JAK2 mutations, JAK inhibitors, such as ruxolitinib, have shown remarkable efficacy in reducing splenomegaly, improving symptoms, and controlling abnormal blood cell counts. Research on new JAK inhibitors brings more selectivity and safety to the development of therapies.

In addition to TKIs and JAK inhibitors, various other targeted therapies are being investigated for myeloid proliferations and neoplasms. These include agents targeting specific downstream signaling molecules, epigenetic modifiers, and immunotherapies.

Our Services

At our company, we pride ourselves on providing cutting-edge diagnostics and therapy development services for myeloid proliferations and neoplasms. Our company focuses on developing novel strategies targeting these abnormal signaling pathways, providing more possibilities for the therapy development of myeloid proliferations and neoplasms.

Our Therapy Development Platforms

The establishment and characterization of animal models that faithfully reproduce the characteristics of myeloid proliferations and neoplasms are our expertise. These models are valuable tools for understanding disease mechanisms, testing drug candidates, and assessing drugs. We conduct rigorous preclinical studies using cell lines, organoids, and experimental animals to evaluate the pharmacokinetics and safety of potential therapies.

If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

Reference

Pizzi, Marco, et al. "The classification of myeloproliferative neoplasms: rationale, historical background and future perspectives with focus on unclassifiable cases." Cancers 13.22 (2021): 5666.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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